MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Autophagy' source. Tue, 07 Feb 2012 08:48:50 +0100 http://www.medworm.com/index.php?rid=5659111&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22301999%26dopt%3DAbstract Authors: Klionsky DJ Abstract In the August 2009 issue of Autophagy, I indicated that we were launching a new category of article, Protocols. At that time, I noted that we would ultimately be placing these articles on a new site online. Well, that time has finally arrived (see www.landesbioscience.com/journals/autophagy/protocols/ for links to these papers). Therefore, it seems appropriate for me to briefly distinguish among three types of community-oriented papers, Protocol, Toolbox and Resource. PMID: 22301999 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5659111 Sun, 05 Feb 2012 07:13:51 +0100 5659111 http://www.medworm.com/index.php?rid=5659110&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22302000%26dopt%3DAbstract Authors: Eisenberg-Lerner A, Kimchi A Abstract Reactive oxygen species (ROS) that accumulate under oxidative pressure cause severe damage to cellular components, and induce various cellular responses, including apoptosis, programmed necrosis and autophagy, depending on the cellular setting. Various studies have described ROS-induced autophagy, but only a few direct factors that regulate autophagy under oxidative stress are known to date. We have identified DAPK and PKD as such regulators by demonstrating their role in the process of autophagy in general, and specifically during oxidative stress. PKD acts as a downstream effector of DAPk in the regulation of autophagy. Furthermore, PKD functions within the autophagic network as an activator of VPS34, by associating with and phosphor... Autophagy journals http://www.medworm.com/rss/comments.php?id=5659110 Sun, 05 Feb 2012 07:13:40 +0100 5659110 http://www.medworm.com/index.php?rid=5659109&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22302001%26dopt%3DAbstract Authors: Jin Y, Tanaka A, Choi AM, Ryter SW Abstract Oxygen (O 2), while essential for aerobic life, can also cause metabolic toxicity through the excess generation of reactive oxygen species (ROS). Pathological changes in ROS production can originate through the partial reduction of O 2 during mitochondrial electron transport, as well as from enzymatic sources. This phenomenon, termed the oxygen paradox, has been implicated in aging and disease, and is especially evident in critical care medicine. Whereas high O 2 concentrations are utilized as a life-sustaining therapeutic for respiratory insufficiency, they in turn can cause acute lung injury. Alveolar epithelial cells represent a primary target of hyperoxia-induced lung injury. Recent studies have indicated that epithelial cell... Autophagy journals http://www.medworm.com/rss/comments.php?id=5659109 Sun, 05 Feb 2012 07:13:30 +0100 5659109 http://www.medworm.com/index.php?rid=5659108&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22302002%26dopt%3DAbstract Authors: Sato M, Sato K Abstract Maternal inheritance of mitochondrial DNA (mtDNA) is generally observed in many eukaryotes. Sperm-derived paternal mitochondria and their mtDNA enter the oocyte cytoplasm upon fertilization and then normally disappear during early embryogenesis. However, the mechanism underlying this clearance of paternal mitochondria has remained largely unknown. Recently, we showed that autophagy is required for the elimination of paternal mitochondria in Caenorhabditis elegans embryos. Shortly after fertilization, autophagosomes are induced locally around the penetrated sperm components. These autophagosomes engulf paternal mitochondria, resulting in their lysosomal degradation during early embryogenesis. In autophagy-defective zygotes, paternal mitochondria and ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5659108 Sun, 05 Feb 2012 07:13:19 +0100 5659108 http://www.medworm.com/index.php?rid=5659107&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22302003%26dopt%3DAbstract In this study we used the unicellular green alga Chlamydomonas reinhardtii to demonstrate that defects in carotenoid biosynthesis lead to the activation of autophagy, a membrane-trafficking process that participates in the recycling and degradation of damaged or toxic cellular components. Carotenoid depletion caused by either the mutation of phytoene synthase or the inhibition of phytoene desaturase by the herbicide norflurazon, resulted in a strong induction of autophagy. We found that high light transiently activates autophagy in wild-type Chlamydomonas cells as part of an adaptation response to this stress. Our results showed that a Chlamydomonas mutant defective in the synthesis of specific carotenoids that accumulate during high light stress exhibits constitutive autophagy. Moreover, ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5659107 Sun, 05 Feb 2012 07:13:09 +0100 5659107 http://www.medworm.com/index.php?rid=5659106&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22302004%26dopt%3DAbstract In this study, a sensitive and specific method to measure the activity of two Atg4 homologs in mammalian cells, Atg4A and Atg4B, was developed using a fluorescence resonance energy transfer (FRET)-based approach. Thus LC3B and GATE-16, two substrates that could be differentially cleaved by Atg4A and Atg4B, were fused with CFP and YFP at the N- and C-terminus, respectively, allowing FRET to occur. The FRET signals decreased in proportion to the Atg4-mediated cleavage, which separated the two fluorescent proteins. This method is highly efficient for measuring the enzymatic activity and kinetics of Atg4A and Atg4B under in vitro conditions. Applications of the assay indicated that the activity of Atg4B was dependent on its catalytic cysteine and expression level, but showed little changes und... Autophagy journals http://www.medworm.com/rss/comments.php?id=5659106 Sun, 05 Feb 2012 07:13:00 +0100 5659106 http://www.medworm.com/index.php?rid=5659105&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22302005%26dopt%3DAbstract In this study, we sought to examine the effect of Andro on autophagy, and to evaluate whether such effect is relevant to the sensitization effect of Andro on apoptosis induced by DNA damage agents in cancer cells. First, we found that Andro is able to significantly enhance autophagic markers in various cancer cell lines, including GFP-LC3 puncta and LC3-II level. Interestingly, Andro treatment also led to marked increase of p62 protein level and addition of chloroquine (CQ) failed to further enhance either LC3-II or p62 level, indicating that Andro is likely to suppress autophagic flux at the maturation and degradation stage. Next, we provided evidence that Andro inhibits autophagosome maturation not by affecting the lysosomal function, but by impairing autophagosome-lysosome fusion. Lastl... Autophagy journals http://www.medworm.com/rss/comments.php?id=5659105 Sun, 05 Feb 2012 07:12:50 +0100 5659105 http://www.medworm.com/index.php?rid=5659104&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22302006%26dopt%3DAbstract Authors: Ma X, Godar RJ, Liu H, Diwan A Abstract Hypoxia-inducible pro-death protein BNIP3 (BCL-2/adenovirus E1B 19-kDa interacting protein 3), provokes mitochondrial permeabilization causing cardiomyocyte death in ischemia-reperfusion injury. Inhibition of autophagy accelerates BNIP3-induced cell death, by preventing removal of damaged mitochondria. We tested the hypothesis that stimulating autophagy will attenuate BNIP3-induced cardiomyocyte death. Neonatal rat cardiac myocytes (NRCMs) were adenovirally transduced with BNIP3 (or LacZ as control; at multiplicity of infection = 100); and autophagy was stimulated with rapamycin (100 nM). Cell death was assessed at 48 h. BNIP3 expression increased autophagosome abundance 8-fold and caused a 3.6-fold increase in cardiomyocyte death as... Autophagy journals http://www.medworm.com/rss/comments.php?id=5659104 Sun, 05 Feb 2012 07:12:40 +0100 5659104 http://www.medworm.com/index.php?rid=5659103&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22302007%26dopt%3DAbstract Authors: Zhang J, Liu J, Liu L, McKeehan WL, Wang F Abstract The fibroblast growth factor (FGF) signaling axis plays important roles in heart development. Yet, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood. Using genetically engineered mouse and in vitro cultured embryoid body (EB) models, we demonstrate that FGF signaling suppresses premature differentiation of heart progenitor cells, as well as autophagy in outflow tract (OFT) myocardiac cells. The FGF also promotes mesoderm differentiation in embryonic stem cells (ESCs) but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, inhibition of FGF signaling increases myocardial differentiation and autophagy in both ex vivo cultured embryos and EBs, wher... Autophagy journals http://www.medworm.com/rss/comments.php?id=5659103 Sun, 05 Feb 2012 07:12:31 +0100 5659103 http://www.medworm.com/index.php?rid=5659102&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22302008%26dopt%3DAbstract Authors: Bhogal RH, Weston CJ, Curbishley SM, Adams DH, Afford SC Abstract The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia-reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found to be key regulators of autophagy. Autophagy involved the upregulation of BECN1, LC3A, Atg7, Atg5 and Atg... Autophagy journals http://www.medworm.com/rss/comments.php?id=5659102 Sun, 05 Feb 2012 07:12:21 +0100 5659102 http://www.medworm.com/index.php?rid=5659101&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22302009%26dopt%3DAbstract Authors: Phadwal K, Alegre-Abarrategui J, Watson AS, Pike L, Anbalagan S, Hammond EM, Wade-Martins R, McMichael A, Klenerman P, Simon AK Abstract Autophagy is a conserved constitutive cellular process, responsible for the degradation of dysfunctional proteins and organelles. Autophagy plays a role in many diseases such as neurodegeneration and cancer; however, to date, conventional autophagy detection techniques are not suitable for clinical samples. We have developed a high throughput, statistically robust technique that quantitates autophagy in primary human leukocytes using the Image stream, an imaging flow cytometer. We validate this method on cell lines and primary cells knocked down for essential autophagy genes. Also, using this method we show that T cells have higher autoph... Autophagy journals http://www.medworm.com/rss/comments.php?id=5659101 Sun, 05 Feb 2012 07:12:11 +0100 5659101 http://www.medworm.com/index.php?rid=5623156&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240588%26dopt%3DAbstract Authors: Cormier O, Mohseni N, Voytyuk I, Reed BH Abstract During Drosophila embryogenesis the majority of the extra-embryonic epithelium known as the amnioserosa (AS) undergoes programmed cell death (PCD) following the completion of the morphogenetic process of dorsal closure. Approximately ten percent of AS cells, however, are eliminated during dorsal closure by extrusion from the epithelium. Using biosensors that report autophagy and caspase activity in vivo, we demonstrate that AS cell extrusion occurs in the context of elevated autophagy and caspase activation. Furthermore, we evaluate AS extrusion rates, autophagy, and caspase activation in embryos in which caspase activity or autophagy are altered by genetic manipulation. This includes using the GAL4/UAS system to drive expr... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623156 Tue, 24 Jan 2012 09:56:18 +0100 5623156 http://www.medworm.com/index.php?rid=5623155&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240589%26dopt%3DAbstract Authors: Singh K, Matsuyama S, Drazba JA, Almasan A Abstract Autophagy regulates cell survival and cell death upon various cellular stresses, yet the molecular signaling events involved are not well defined. Here, we established the function of a proteolytic Cyclin E fragment (p18-CycE) in DNA damage-induced autophagy, apoptosis, and senescence. p18-CycE was identified in hematopoietic cells undergoing DNA damage-induced apoptosis. In epithelial cells exposed to DNA damage, chronic but not transient expression of p18-CycE leads to higher turnover of LC3 I/II and increased emergence of autophagosomes and autolysosomes. Levels of p18-CycE, which was generated by proteolytic cleavage of endogenous Cyclin E, were greatly increased by chloroquine and correlated with LC 3II conversion. P... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623155 Tue, 24 Jan 2012 09:56:09 +0100 5623155 http://www.medworm.com/index.php?rid=5623154&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240590%26dopt%3DAbstract Authors: Vázquez P, Arroba AI, Cecconi F, de la Rosa EJ, Boya P, De Pablo F Abstract Neuroepithelial cells undergoing differentiation efficiently remodel their cytoskeleton and shape in an energy-consuming process. The capacity of autophagy to recycle cellular components and provide energy could fulfill these requirements, thus supporting differentiation. However, little is known regarding the role of basal autophagy in neural differentiation. Here we report an increase in the expression of the autophagy genes Atg7, Becn1, Ambra1 and LC3 in vivo in the mouse embryonic olfactory bulb (OB) during the initial period of neuronal differentiation at E15.5, along with a parallel increase in neuronal markers. In addition, we observed an increase in LC3 lipidation and autophagic flux durin... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623154 Tue, 24 Jan 2012 09:56:00 +0100 5623154 http://www.medworm.com/index.php?rid=5623153&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240591%26dopt%3DAbstract Authors: Nakatogawa H, Ishii J, Asai E, Ohsumi Y Abstract Atg8 is a ubiquitin-like protein required for autophagy in the budding yeast Saccharomyces cerevisiae. A ubiquitin-like system mediates the conjugation of the C terminus of Atg8 to the lipid phosphatidylethanolamine (PE), and this conjugate (Atg8-PE) plays a crucial role in autophagosome formation at the pre-autophagosomal structure (PAS). The cysteine protease Atg4 processes the C terminus of newly-synthesized Atg8 and also delipidates Atg8 to release the protein from membranes. While the former is prerequisite for lipidation of Atg8, the significance of the latter in autophagy has remained unclear. Here, we show that autophagosome formation is significantly retarded in cells deficient for Atg4-mediated delipidation of Atg8... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623153 Tue, 24 Jan 2012 09:55:50 +0100 5623153 http://www.medworm.com/index.php?rid=5623152&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240663%26dopt%3DAbstract Authors: Josefsen L, Droce A, Sondergaard TE, Sørensen JL, Bormann J, Schäfer W, Giese H, Olsson S Abstract The role of autophagy in necrotrophic fungal physiology and infection biology is poorly understood. We have studied autophagy in the necrotrophic plant pathogen Fusarium graminearum in relation to development of nonassimilating structures and infection. We identified an ATG8 homolog F. graminearum ATG8 whose first 116 amino acids before the predicted ATG4 cleavage site are 100% identical to Podospora anserina ATG8. We generated a ΔFgatg8 mutant by gene replacement and showed that this cannot form autophagic compartments. The strain forms no perithecia, has reduced conidia production and the aerial mycelium collapses after a few days in culture. The collapsing aerial myceli... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623152 Tue, 24 Jan 2012 09:55:41 +0100 5623152 http://www.medworm.com/index.php?rid=5623151&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240664%26dopt%3DAbstract Authors: Zhou WH, Tang F, Xu J, Wu X, Yang SB, Feng ZY, Ding YG, Wan XB, Guan Z, Li HG, Lin DJ, Shao CK, Liu Q Abstract Recent studies have suggested that dysregulation of autophagy plays a pivotal role in tumorigenesis. Here, we determined the prognostic value of autophagy-related protein Beclin 1 in gastric cancer. A total of 153 primary gastric cancer patients were subjected to analysis of Beclin 1 expression and survival prognosis. Among them, 68 patients were assigned randomly and used as a training set to generate a cutoff score for Beclin 1 expression by receive operating characteristic (ROC) curve analysis. The ROC-generated cutoff score was subjected to analyze the association of Beclin 1 with clinical characteristics and patient outcome. In a testing set (n = 85) and over... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623151 Tue, 24 Jan 2012 09:55:32 +0100 5623151 http://www.medworm.com/index.php?rid=5623149&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248716%26dopt%3DAbstract This study addresses the function of autophagy in neurodegeneration that has been induced by acute focal cerebellar lesions. We provide morphological, ultrastructural, and biochemical evidence that lesions in a cerebellar hemisphere activates autophagy in axotomized precerebellar neurons. Through time course analyses of the apoptotic cascade, we determine mitochondrial dysfunction to be the early trigger of degeneration. Further, the stimulation of autophagy by rapamycin and the employment of mice with impaired autophagic responses allowed to demonstrate that autophagy protects from damage promoting functional recovery. These findings have therapeutic significance, demonstrating the potential of pro-autophagy treatments for acute brain pathologies, such as stroke and brain trauma. PMID... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623149 Tue, 24 Jan 2012 09:55:22 +0100 5623149 http://www.medworm.com/index.php?rid=5623130&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248717%26dopt%3DAbstract Authors: Klionsky DJ PMID: 22248717 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5623130 Tue, 24 Jan 2012 09:55:13 +0100 5623130 http://www.medworm.com/index.php?rid=5623129&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248718%26dopt%3DAbstract Authors: Korkmaz G, le Sage C, Tekirdag KA, Agami R, Gozuacik D Abstract Macroautophagy (autophagy) is the major intracellular degradation pathway for long-lived proteins and organelles. It helps the cell to survive a spectrum of stressful conditions including starvation, growth factor deprivation and misfolded protein accumulation. Moreover, abnormalities of autophagy play a role in major health problems including cancer and neurodegenerative diseases. Yet, mechanisms controlling autophagic activity are not fully understood. Here, we describe hsa-miR-376b (miR-376b) as a new microRNA (miRNA) regulating autophagy. We showed that miR-376b expression attenuated starvation- and rapamycin-induced autophagy in MCF-7 and Huh-7 cells. We discovered autophagy proteins ATG4C and BECN1 (Becl... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623129 Tue, 24 Jan 2012 09:55:03 +0100 5623129 http://www.medworm.com/index.php?rid=5623128&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22252008%26dopt%3DAbstract Authors: Maycotte P, Aryal S, Cummings CT, Thorburn J, Morgan MJ, Thorburn A Abstract Chloroquine (CQ) is a 4-aminoquinoline drug used for the treatment of diverse diseases. It inhibits lysosomal acidification and therefore prevents autophagy by blocking autophagosome fusion and degradation. In cancer treatment, CQ is often used in combination with chemotherapeutic drugs and radiation because it has been shown to enhance the efficacy of tumor cell killing. Since CQ and its derivatives are the only inhibitors of autophagy that are available for use in the clinic, multiple ongoing clinical trials are currently using CQ or hydroxychloroquine (HCQ) for this purpose, either alone, or in combination with other anticancer drugs. Here we show that in the mouse breast cancer cell lines, 67N... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623128 Tue, 24 Jan 2012 09:54:53 +0100 5623128 http://www.medworm.com/index.php?rid=5623127&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22252009%26dopt%3DAbstract We report that serum and amino acids withdrawal is accompanied by a rapid increase of autophagosome formation but also by a slower induction of the expression of several autophagy-related genes (LC3B, gabarapl1, atg4b). We also showed that this latter response is controlled by amino acid (AA) availability and that both TOR-dependent and TOR-independent pathways are involved in this effect. Together these results suggest an important role for AA released by muscle proteolysis during the fasting period in regulating the subtle balance between using proteins as disposable furniture to provide energy, and conserving muscle through protein sparing. PMID: 22252009 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5623127 Tue, 24 Jan 2012 09:54:42 +0100 5623127 http://www.medworm.com/index.php?rid=5623126&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22258091%26dopt%3DAbstract Authors: West RJ, Sweeney ST Abstract Many neurodegenerative conditions have oxidative stress burdens where levels of reactive oxygen species (ROS) exceed the antioxidant capacity of the neuron. ROS can induce wide-ranging damage in a cell and this is prevented by the activation of antioxidant responses including autophagy. Jun-kinase (JNK) is stimulated by ROS and mediates antioxidant responses via the activation of the transcriptional activators Fos and Jun (AP-1). In recently published work we examined Drosophila mutants with overgrown larval neuromuscular synapses, mutants that also show all the hallmarks of lysosomal storage disease (LSD). We find that we can reverse this synaptic overgrowth by reducing the oxidative stress burden, and that synaptic overgrowth is mediated by a... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623126 Tue, 24 Jan 2012 09:54:32 +0100 5623126 http://www.medworm.com/index.php?rid=5623125&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22258092%26dopt%3DAbstract Authors: Yin JJ, Li YB, Wang Y, Liu GD, Wang J, Zhu XO, Pan SH Abstract In pancreatic β-cells, the endoplasmic reticulum (ER) is the crucial site for insulin biosynthesis, as this is where the protein-folding machinery for secretory proteins is localized. Perturbations to ER function of the β-cell, such as those caused by high levels of free fatty acid and insulin resistance, can lead to an imbalance in protein homeostasis and ER stress, which has been recognized as an important mechanism for type 2 diabetes. Macroautophagy (hereafter referred to as autophagy) is activated as a novel signaling pathway in response to ER stress. In this review, we outline the mechanism of ER stress-mediated β-cell death and focus on the role of autophagy in ameliorating ER stress. The development ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623125 Tue, 24 Jan 2012 09:54:22 +0100 5623125 http://www.medworm.com/index.php?rid=5623124&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22258093%26dopt%3DAbstract In this study, we aimed to establish a cell-free assay recapitulating leucine-mediated autophagy in vitro and dissect its biochemical requirement. We found that in a cell-free assay, membrane association of Barkor/Atg14(L), a specific autophagosome-binding protein, is suppressed by cytosol from nutrient-rich medium and such suppression is released by nutrient deprivation. We also showed that rapamycin could efficiently reverse the suppression of nutrient rich cytosol, suggesting an essential role of mTORC1 in autophagy inhibition in this cell-free system. Furthermore, we demonstrated that leucine supplementation in the cultured cells blocks Barkor puncta formation and autophagy activity. Hence, we establish a novel cell-free assay recapitulating leucine-mediated autophagy inhibition in an ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5623124 Tue, 24 Jan 2012 09:54:11 +0100 5623124 http://www.medworm.com/index.php?rid=5535161&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22170150%26dopt%3DAbstract Authors: Wang JH, Behrns KE, Leeuwenburgh C, Kim JS Abstract A steady increase in life expectancy has resulted in an equivalent increase in elderly patients who are more susceptible to diseases than young patients. In a recent study, we found that in both in vitro and in vivo models of ischemia/reperfusion (I/R), a loss of ATG4B is causatively associated with the increased sensitivity of the liver to I/R injury with age. Our work suggests that a restoration or enhancement of autophagy is a novel therapeutic modality to ameliorate liver function after I/R to aged livers. PMID: 22170150 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5535161 Fri, 23 Dec 2011 23:43:20 +0100 5535161 http://www.medworm.com/index.php?rid=5535160&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22170151%26dopt%3DAbstract Authors: Tanida I, Yamasaki M, Komatsu M, Ueno T Abstract ATG7 is an autophagy-related E1-like enzyme that is essential for two ubiquitination-like reactions, ATG12-conjugation and LC3-lipidation. The existence of functional sequences at the amino-terminal region of human ATG7 remains uncertain. Mutational analyses of ATG7 revealed that both mutant ATG7ΔFAP lacking the FAP motif and ATG7FAPtoDDD, in which the Phe15-Ala16-Pro17 sequence was changed to Asp-Asp-Asp, could not complement defects in endogenous ATG12-conjugation and LC3-lipidation when expressed in Atg7-deficient mouse embryonic fibroblasts (MEFs). However, wild-type ATG7 complemented the defects in these cells. Overexpression of GFP-ATG10 and GFP-ATG12 rescued a defect in ATG12-conjugation in Atg7-deficient MEFs expres... Autophagy journals http://www.medworm.com/rss/comments.php?id=5535160 Fri, 23 Dec 2011 23:43:10 +0100 5535160 http://www.medworm.com/index.php?rid=5535159&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22170152%26dopt%3DAbstract Authors: Graziotto JJ, Cao K, Collins FS, Krainc D Abstract While rapamycin has been in use for years in transplant patients as an antirejection drug, more recently it has shown promise in treating diseases of aging, such as neurodegenerative disorders and atherosclerosis. We recently reported that rapamycin reverses the cellular phenotype of fibroblasts from children with the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). We found that the causative aberrant protein, progerin, was cleared through autophagic mechanisms when the cells were treated with rapamycin, suggesting a new potential treatment for HGPS. Recent evidence shows that progerin is also present in aged tissues of healthy individuals, suggesting that progerin may contribute to physiological aging... Autophagy journals http://www.medworm.com/rss/comments.php?id=5535159 Fri, 23 Dec 2011 23:43:01 +0100 5535159 http://www.medworm.com/index.php?rid=5535158&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22170153%26dopt%3DAbstract Authors: Mai S, Muster B, Bereiter-Hahn J, Jendrach M Abstract Mitochondrial health is maintained by the quality control mechanisms of mitochondrial dynamics (fission and fusion) and mitophagy. Decline of these processes is thought to contribute to aging and neurodegenerative diseases. To investigate the role of mitochondrial quality control in aging on the cellular level, human umbilical vein endothelial cells (HUVEC) were subjected to mitochondria-targeted damage by combining staining of mitochondria and irradiation. This treatment induced a short boost of reactive oxygen species, which resulted in transient fragmentation of mitochondria followed by mitophagy, while mitochondrial dynamics were impaired. Furthermore, targeted mitochondrial damage upregulated autophagy factors LC3B... Autophagy journals http://www.medworm.com/rss/comments.php?id=5535158 Fri, 23 Dec 2011 23:42:51 +0100 5535158 http://www.medworm.com/index.php?rid=5535157&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22170154%26dopt%3DAbstract Authors: Cheong H, Lindsten T, Thompson CB Abstract Autophagy plays an important role in the cellular response to a variety of metabolic stress conditions thus contributing to the maintenance of intracellular homeostasis. Studies in yeast have defined the genetic components involved in the initiation of autophagy as well as the progression through the autophagic cascade. The yeast kinase Atg1 initiates autophagy in response to nutrient limitation in a TOR-dependent manner. The ulk family of genes encodes the mammalian orthologue of yeast Atg1. Our recent work using mouse embryonic fibroblast (MEF) cell lines deficient for both ulk1 and ulk2, has revealed that autophagy induction is more complex in mammals than in yeast. Furthermore, these data confirm the surprising finding that a ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5535157 Fri, 23 Dec 2011 23:42:42 +0100 5535157 http://www.medworm.com/index.php?rid=5535156&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22170155%26dopt%3DAbstract Authors: Wirawan E, Lippens S, Vanden Berghe T, Romagnoli A, Fimia GM, Piacentini M, Vandenabeele P Abstract Beclin1(Atg6) is a well-known key regulator of autophagy. Although Beclin1 is enzymatically inert, it governs the autophagic process by regulating PtdIns3KC3-dependent generation of phosphatidylinositol3-phosphate (PtdIns(3)P) and the subsequent recruitment of additional Atg proteins that orchestrate autophagosome formation. Furthermore, Beclin1 is implicated in numerous biological processes, including adaptation to stress, development, endocytosis, cytokinesis, immunity, tumorigenesis, ageing and cell death. Whether all of these processes involve only the autophagy-inducing function of Beclin1 is now being seriously questioned, because Beclin1 appears to exercise several no... Autophagy journals http://www.medworm.com/rss/comments.php?id=5535156 Fri, 23 Dec 2011 23:42:31 +0100 5535156 http://www.medworm.com/index.php?rid=5535155&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22186228%26dopt%3DAbstract Authors: Lapierre LR, Meléndez A, Hansen M Abstract The cellular recycling process of autophagy is emerging as a central player in many of the conserved longevity pathways in C. elegans, but the underlying mechanisms that link autophagy and life span remain unclear. In a recent study, we provided evidence to suggest that autophagy modulates aging through an effect on lipid homeostasis. Specifically, we identified a role for autophagy in a longevity model in which germline removal in C. elegans extends life span. Life-span extension in these animals is achieved, at least in part, through increased expression of the lipase LIPL-4. We found that autophagy and LIPL-4-dependent lipolysis are both upregulated in germline-less animals and work interdependently to prolong life span. While... Autophagy journals http://www.medworm.com/rss/comments.php?id=5535155 Fri, 23 Dec 2011 23:42:21 +0100 5535155 http://www.medworm.com/index.php?rid=5535154&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22186229%26dopt%3DAbstract Authors: Ding Y, Sun X, Xu X Abstract The target of rapamycin (TOR) kinase is part of an evolutionarily conserved signaling pathway that coordinates cell growth, survival, and autophagy. Previously, pharmacological studies using rapamycin have suggested a cardioprotective effect of TOR signaling inhibition on cardiomyopathy. We found that rapamycin exerts a conserved cardioprotective effect in two adult zebrafish models of cardiomyopathy of different etiology, and provided the first genetic evidence to support a long-term cardioprotective effect of TOR signaling inhibition. Moreover, we detected dynamic TOR-autophagy activities along different stages of cardiomyopathy. This needs to be considered when developing TOR-autophagy-based therapeutics for cardiomyopathy. PMID: 2218622... Autophagy journals http://www.medworm.com/rss/comments.php?id=5535154 Fri, 23 Dec 2011 23:42:12 +0100 5535154 http://www.medworm.com/index.php?rid=5475510&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22108005%26dopt%3DAbstract Authors: Zhan Z, Li Q, Wu P, Ye Y, Tseng HY, Zhang L, Zhang XD Abstract Autophagy-associated release of HMGB1 is known to protect cancer cells from many chemotherapeutics. However, the detailed molecular mechanism(s) responsible remains largely undefined. We show in this study that HMGB1 released into the extracellular space protects gastric cancer cells from apoptosis induced by the microtubule-targeting drug vincristine through transcriptional upregulation of Mcl-1. Extracellular HMGB1 appeared essential for autophagy-mediated inhibition of apoptosis, in that siRNA knockdown of HMGB1 or inhibition of its release abolished the protective effect of autophagy. Strikingly, vincristine upregulated the Mcl-1 mRNA expression through a transcriptional increase, but did not alter the expr... Autophagy journals http://www.medworm.com/rss/comments.php?id=5475510 Tue, 06 Dec 2011 12:12:56 +0100 5475510 http://www.medworm.com/index.php?rid=5475509&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22108006%26dopt%3DAbstract Authors: de la Cruz-Morcillo MA, Sánchez-Prieto R Abstract There have been strange couples throughout history, which have behaved in an opposite manner while sharing the same space, with, in our opinion, Jack Lemon and Walter Matthau (the "Odd Couple") being one of the best examples. Most biological processes are interconnected with each other, and the imbalance in favor of one or another always involves biological changes. In the case of cell death by genotoxic stress, there are two main actors who seem to have a decisive role: apoptosis and autophagy. We have recently shown how a MAPK signaling pathway, the p38 pathway, may be controlling the balance of both processes in genotoxic stress conditions triggered by a therapeutic agent commonly used in cancer therapy such as 5-fluoro... Autophagy journals http://www.medworm.com/rss/comments.php?id=5475509 Tue, 06 Dec 2011 12:12:47 +0100 5475509 http://www.medworm.com/index.php?rid=5475508&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22108007%26dopt%3DAbstract Authors: Xing S, Zhang Y, Li J, Zhang J, Li Y, Dang C, Li C, Fan Y, Yu J, Pei Z, Zeng J Abstract Cerebral infarction can cause secondary degeneration of thalamus and delay functional recovery. However, the mechanisms underlying secondary degeneration are unclear. The present study aimed to determine the occurrence and contribution of autophagy to the thalamic degeneration after cerebral infarction. Focal cerebral infarction was induced by distal middle cerebral artery occlusion (MCAO). Autophagic activation, Beclin 1 expression and amyloid β (Aβ) deposits were determined by immunofluorescence, immunoblot and electron microscopy. Secondary damage to thalamus was assessed with Nissl staining and immunofluorescence analysis. Apoptosis was determined using TUNEL staining. The contrib... Autophagy journals http://www.medworm.com/rss/comments.php?id=5475508 Tue, 06 Dec 2011 12:12:38 +0100 5475508 http://www.medworm.com/index.php?rid=5475507&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113201%26dopt%3DAbstract Authors: Zhai P, Sadoshima J Abstract Autophagy is a catabolic process that degrades long-lived proteins, pathogens and damaged organelles. Autophagy is active in the heart at baseline and is further stimulated by stresses, such as nutrient starvation, ischemia/reperfusion (I/R) and heart failure. Baseline autophagy plays an adaptive role in the heart, and contributes to the maintenance of cardiac structure and function and the inhibition of age-associated abnormalities, by achieving quality control of proteins and organelles. Activation of autophagy during ischemia is beneficial because it improves cell survival and cardiac function. However, excessive autophagy with robust upregulation of BECN1 during reperfusion appears to enhance cell death, which is detrimental to the heart. W... Autophagy journals http://www.medworm.com/rss/comments.php?id=5475507 Tue, 06 Dec 2011 12:12:30 +0100 5475507 http://www.medworm.com/index.php?rid=5475506&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113202%26dopt%3DAbstract Authors: Lu JH, Tan JQ, Durairajan SS, Liu LF, Zhang ZH, Ma L, Shen HM, Chan HY, Li M Abstract Accumulation of α-synuclein (α-syn) in the brain is a pathogenic feature and also a causative factor of Parkinson disease. Isorhynchophylline (IsoRhy) is a major tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.)Jacks (Gouteng in Chinese), which has been used for the treatment of neurological diseases in East Asia for centuries. Here we report a novel function of IsoRhy as a neuronal autophagy inducer. IsoRhy induced autophagy in different neuronal cell lines, including N2a, SH-SY5Y and PC12 cells, and also in primary cortical neurons. Furthermore, IsoRhy induced autophagy in the fat bodies of Drosophila. IsoRhy promoted clearance of wil... Autophagy journals http://www.medworm.com/rss/comments.php?id=5475506 Tue, 06 Dec 2011 12:12:21 +0100 5475506 http://www.medworm.com/index.php?rid=5475505&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113203%26dopt%3DAbstract This study was taken to determine the involvement of autophagy in neuroprotection of Nampt in cerebral ischemia. Middle cerebral artery occlusion (MCAO) in rats and oxygen-glucose deprivation (OGD) in cultured cortical neurons were performed. Nampt was overexpressed or knocked-down using lentivirus-mediated gene transfer in vivo and in vitro. Immunochemistry (LC3-II), electron microscope and immunoblotting assays (LC3-II, beclin-1, mammalian target of rapamycin [mTOR], S6K1 and tuberous sclerosis complex-2 [TSC2]) were performed to assess autophagy. We found that overexpression of Nampt increased autophagy (LC3 puncta immunochemistry staining, LC3-II/beclin-1 expression and autophagosomes number) both in vivo and in vitro at 2 hours after MCAO. At the early stage of OGD, autophagy inducer ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5475505 Tue, 06 Dec 2011 12:12:11 +0100 5475505 http://www.medworm.com/index.php?rid=5421280&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082869%26dopt%3DAbstract Authors: Nair U, Klionsky DJ Abstract Skeletal muscle fibers of collagen VI null (Col6a1 (-/-) ) mice show signs of degeneration due to a block in autophagy, leading to the accumulation of damaged mitochondria and excessive apoptosis. Attempts to induce autophagic flux by subjecting these mutant mice to long-term or shorter bursts of physical activity are unsuccessful. In normal mice, the induction of autophagy in the skeletal muscles post-exercise is able to prevent the accumulation of damaged organelles and maintain cellular homeostasis. Thus, these studies provide an important connection between autophagy and exercise physiology. PMID: 22082869 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5421280 Fri, 18 Nov 2011 23:56:08 +0100 5421280 http://www.medworm.com/index.php?rid=5421279&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082870%26dopt%3DAbstract Authors: Gottlieb RA, Mentzer RM, Linton PJ Abstract Recent publications link mitophagy mediated by PINK1 and Parkin with cardioprotection and attenuation of inflammation and cell death. The field is in need of methods to monitor mitochondrial turnover in vivo to support the development of new therapies targeting mitochondrial turnover. PMID: 22082870 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5421279 Fri, 18 Nov 2011 23:56:00 +0100 5421279 http://www.medworm.com/index.php?rid=5421278&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082871%26dopt%3DAbstract Authors: Hu Z, Zhang J, Zhang Q Abstract The implications of autophagy related genes in serious neural degenerative diseases have been well documented. However, the functions and regulation of the family genes in embryonic development remain to be rigorously studied. Here, we make the first report on the important role of atg5 gene in zebrafish neurogenesis and organogenesis as evidenced by the spatiotemporal expression pattern and functional analysis. Using morpholino oligo knockdown and mRNA overexpression, we demonstrate that zebrafish atg5 is required for normal morphogenesis of brain regionalization and body plan as well as for expression regulation of neural gene markers: gli1, huC, nkx2.2, pink1, β-synuclein, xb51 and zic1. We further demonstrate that ATG5 protein is involv... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421278 Fri, 18 Nov 2011 23:55:51 +0100 5421278 http://www.medworm.com/index.php?rid=5421277&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082872%26dopt%3DAbstract In this study we identified a novel isoform of mammalian Atg16L, termed Atg16L2, that consists of the same domain structures as Atg16L1. Biochemical analysis revealed that Atg16L2 interacts with Atg5 and self-oligomerizes to form an ~800-kDa complex, the same as Atg16L1 does. A subcelluar distribution analysis indicated that, despite forming the Atg12-5-16L2 complex, Atg16L2 is not recruited to isolation membranes and is mostly present in the cytosol. The results also showed that Atg16L2 is unable to compensate for the function of Atg16L1 in autophagosome formation, and knockdown of endogenous Atg16L2 did not affect autophagosome formation, indicating that Atg16L2 does not possess the ability to mediate canonical autophagy. Moreover, a chimeric analysis between Atg16L1 and Atg16L2 revealed... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421277 Fri, 18 Nov 2011 23:55:42 +0100 5421277 http://www.medworm.com/index.php?rid=5421276&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082873%26dopt%3DAbstract IP 3 receptor-mediated Ca ( 2+) signaling and autophagy induction are interrelated. Autophagy. 2011 Dec 1;7(12) Authors: Decuypere JP, Welkenhuyzen K, Luyten T, Ponsaerts R, Dewaele M, Molgó J, Agostinis P, Missiaen L, De Smedt H, Parys JB, Bultynck G Abstract The role of intracellular Ca ( 2+) signaling in starvation-induced autophagy remains unclear. Here, we examined Ca ( 2+) dynamics during starvation-induced autophagy and the underlying molecular mechanisms. Tightly correlating with autophagy stimulation, we observed a remodeling of the Ca ( 2+) signalosome. Firstly, short periods of starvation (1 to 3 hr) caused a prominent increase of the ER Ca ( 2+) -store content and enhanced agonist-induced Ca ( 2+) release. The mechanism involved the upregulation of intraluminal... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421276 Fri, 18 Nov 2011 23:55:32 +0100 5421276 http://www.medworm.com/index.php?rid=5421275&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082874%26dopt%3DAbstract We examined the expression of p62 and autophagy markers in the chronically compressed spinal cord of tiptoe-walking Yoshimura mice. In addition, we examined the expression and roles of p62 and autophagy in hypoxic neuronal cells. Western blot analysis showed the accumulation of p62, ubiquitinated proteins, and microtubule-associated protein 1 light chain 3 (LC3), an autophagic marker, in the compressed spinal cord. Immunohistochemical examinations showed that p62 accumulated in neurons, axons, astrocytes, and oligodendrocytes. Electron microscopy showed the expression of autophagy markers, including autolysosomes and autophagic vesicles, in the compressed spinal cord. These findings suggest the presence of p62 and autophagy in the degenerated compressed spinal cord. Hypoxic stress increase... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421275 Fri, 18 Nov 2011 23:55:23 +0100 5421275 http://www.medworm.com/index.php?rid=5421274&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082875%26dopt%3DAbstract Authors: Mauthe M, Jacob A, Freiberger S, Hentschel K, Stierhof YD, Codogno P, Proikas-Cezanne T Abstract Canonical autophagy is positively regulated by the Beclin 1/phosphatidylinositol 3-kinase class III (PtdIns3KC3) complex that generates an essential phospholipid, phosphatidylinositol 3-phosphate (PtdIns(3)P), for the formation of autophagosomes. Previously, we identified the human WIPI protein family and found that WIPI-1 specifically binds PtdIns(3)P, accumulates at the phagophore and becomes a membrane protein of generated autophagosomes. Combining siRNA-mediated protein downregulation with automated high through-put analysis of PtdIns(3)P-dependent autophagosomal membrane localization of WIPI-1, we found that WIPI-1 functions upstream of both Atg7 and Atg5, and stimulates a... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421274 Fri, 18 Nov 2011 23:55:13 +0100 5421274 http://www.medworm.com/index.php?rid=5421273&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082958%26dopt%3DAbstract Authors: Dortet L, Mostowy S, Cossart P Abstract Autophagy is a cell-autonomous mechanism of innate immunity that protects the cytosol against bacterial infection. Invasive bacteria, including Listeria monocytogenes, have thus evolved strategies to counteract a process that limits their intracellular growth. ActA is a surface protein produced by L. monocytogenes to polymerize actin and mediate intra- and intercellular movements, which plays a critical role in autophagy escape. We have recently investigated the role of another L. monocytogenes surface protein, the internalin InlK, in the infection process. We showed that in the cytosol of infected cells, InlK interacts with the Major Vault Protein (MVP), the main component of cytoplasmic ribonucleoprotein particles named vaults. Alt... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421273 Fri, 18 Nov 2011 23:55:04 +0100 5421273 http://www.medworm.com/index.php?rid=5421272&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082959%26dopt%3DAbstract Authors: Wei H, Guan JL Abstract Autophagy is a highly conserved catabolic cellular process by which cells degrade intracellular constituents in lysosomes, and its dysfunctions have been associated with a variety of human diseases including cancer. Previous studies have linked autophagy to both tumor-suppressive and promoting functions in different contexts, although the pro-tumorigenic function of autophagy has not been examined directly in breast or other cancers in animal models with intact immune functions in vivo. FIP200 (focal adhesion kinase family interacting protein of 200 kD) is a component of the ULK1-Atg13-FIP200-Atg101 complex that is essential for the induction of mammalian autophagy. In our recent study, we show that conditional knockout (KO) of FIP200 in the well-ch... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421272 Fri, 18 Nov 2011 23:54:54 +0100 5421272 http://www.medworm.com/index.php?rid=5421271&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082960%26dopt%3DAbstract Authors: Thoen LF, Guimarães EL, van Grunsven LA Abstract Hepatic stellate cell (HSC) activation, the transition from a resident quiescent HSC to a myofibroblastic collagen-producing HSC, is a fundamental feature of liver fibrosis. Autophagy has been implicated in major liver pathologies, such as HCV infection and hepatocarcinoma. However, its role in HSC biology is largely unknown. Recently, we were able to demonstrate that HSC activation is followed by an increased autophagic flux and that its inhibition can partially inhibit the HSC myofibroblastic transition. These results point to autophagy as a possible target in the prevention of HSC activation. PMID: 22082960 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5421271 Fri, 18 Nov 2011 23:54:45 +0100 5421271 http://www.medworm.com/index.php?rid=5421270&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082961%26dopt%3DAbstract Authors: Alibhoy AA, Giardina BJ, Dunton DD, Chiang HL Abstract When Saccharomyces cerevisiae is starved of glucose, the gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase), malate dehydrogenase (MDH2), isocitrate lyase (Icl1) and phosphoenolpyruvate carboxykinase (Pck1) are induced. However, when glucose is added to prolonged starved cells, these enzymes are degraded in the vacuole via the vacuole import and degradation (Vid) pathway. Recent evidence suggests that the Vid pathway merges with the endocytic pathway at actin patches where endocytic vesicles are formed. The convergence of the Vid pathway with the endocytic pathway allows cells to remove intracellular and extracellular proteins simultaneously. However, the genes that regulate this step of the convergence have no... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421270 Fri, 18 Nov 2011 23:54:37 +0100 5421270 http://www.medworm.com/index.php?rid=5421269&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082962%26dopt%3DAbstract Authors: Ma D, Lin JD Abstract Temporal organization of nutrient and energy metabolism is important for maintaining homeostasis in mammals. Autophagy is a conserved cellular pathway that is activated in response to nutrient limitation, resulting in the degradation of cytoplasmic components and the release of amino acids and other nutrients. Recently, we reported that autophagy exhibits robust circadian rhythm in mouse liver, accompanied by cyclic induction of genes involved in various steps of autophagy. Rhythmic activation of physiological autophagy appears to be regulated by transcription factor C/EBPβ, which is sufficient and required for nutritional and circadian regulation of autophagy gene expression. These findings provide new insight into transcriptional control of autopha... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421269 Fri, 18 Nov 2011 23:54:28 +0100 5421269 http://www.medworm.com/index.php?rid=5421268&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082963%26dopt%3DAbstract We report here that DRAM-1 encodes not just one mRNA, but a series of p53-inducible splice variants which are expressed at varying levels in multiple human and mouse cell lines. Two of these new splice variants, termed SV4 and SV5, result in mature mRNA species. Different to 'full-length' DRAM-1 (SV1), SV4 and SV5 do not localise to lysosomes or endosomes, but instead partially localise to peroxisomes and autophagosomes respectively. In addition, SV4 and SV5 can also be found co-localised with certain markers of the endoplasmic reticulum. Similar to SV1, SV4 and SV5 do not appear to be inducers of programmed cell death, but they do modulate autophagy. In summary, these findings identify new autophagy regulators that provide insight into the control of autophagy downstream of p53. PMID:... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421268 Fri, 18 Nov 2011 23:54:20 +0100 5421268 http://www.medworm.com/index.php?rid=5421267&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082964%26dopt%3DAbstract Authors: Shen S, Kepp O, Kroemer G Abstract In the mammalian system, cell death is often preceded or accompanied by autophagic vacuolization, a finding that initially led to the widespread belief that so-called "autophagic cell death" would be mediated by autophagy. Thanks to the availability of genetic tools to disable the autophagic machinery, it has become clear over recent years that autophagy usually constitutes a futile attempt of dying cells to adapt to lethal stress rather than a mechanism to execute a cell death program. Recently, we systematically addressed the question as to whether established or prospective anticancer agents may induce "autophagic cell death". Although a considerable portion among the 1,400 compounds that we evaluated induced autophagic puncta and actu... Autophagy journals http://www.medworm.com/rss/comments.php?id=5421267 Fri, 18 Nov 2011 23:54:11 +0100 5421267 http://www.medworm.com/index.php?rid=5361320&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024743%26dopt%3DAbstract Authors: Alers S, Löffler AS, Paasch F, Dieterle AM, Keppeler H, Lauber K, Campbell DG, Fehrenbacher B, Schaller M, Wesselborg S, Stork B Abstract Under normal growth conditions the mammalian target of rapamycin complex 1 (mTORC1) negatively regulates the central autophagy regulator complex consisting of Unc-51-like kinases 1/2 (Ulk1/2), focal adhesion kinase family-interacting protein of 200 kDa (FIP200) and Atg13. Upon starvation, mTORC1-mediated repression of this complex is released, which then leads to Ulk1/2 activation. In this scenario, Atg13 has been proposed as an adaptor mediating the interaction between Ulk1/2 and FIP200 and enhancing Ulk1/2 kinase activity. Using Atg13-deficient cells, we demonstrate that Atg13 is indispensable for autophagy induction. We further show ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361320 Mon, 31 Oct 2011 21:22:22 +0100 5361320 http://www.medworm.com/index.php?rid=5361319&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024744%26dopt%3DAbstract Authors: Nair U, Klionsky DJ Abstract We recently showed that phagophore biogenesis requires SNAREs. Our data indicate that the exocytic Q/t-SNAREs Sso1/2 and Sec9 are required for one of the earliest steps in autophagosome biogenesis, the homotypic fusion of Atg9-containing vesicles. We propose that this step precedes the formation of Atg9-containing tubulovesicular clusters (TVCs) that is a key step in perivacuolar, phagophore assembly. We also found that the endosomal Q/t-SNARE Tlg2 and the R/v-SNAREs Sec22 and Ykt6 interact with Sso1-Sec9, and are required for normal Atg9 trafficking. Thus, autophagosome biogenesis appears to involve multiple SNARE-mediated fusion events. These findings provide novel insights into the mechanism of autophagosome construction. PMID: 22024744 ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361319 Mon, 31 Oct 2011 21:22:12 +0100 5361319 http://www.medworm.com/index.php?rid=5361318&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024745%26dopt%3DAbstract Authors: Rambold AS, Kostelecky B, Lippincott-Schwartz J Abstract Starvation induces a protective process of self-cannibalization called autophagy that is thought to mediate non-selective degradation of cytoplasmic material. We recently reported that mitochondria escape autophagosomal degradation through extensive fusion into mitochondrial networks upon certain starvation conditions. The extent of mitochondrial elongation is dependent on the type of nutrient deprivation, with amino acid depletion having a particularly strong effect. Downregulation of the mitochondrial fission protein Drp1 was determined to be important in bringing about starvation-induced mitochondrial fusion. The formation of mitochondrial networks during nutrient depletion selectively blocked their autophagic deg... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361318 Mon, 31 Oct 2011 21:22:02 +0100 5361318 http://www.medworm.com/index.php?rid=5361317&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024746%26dopt%3DAbstract Authors: Hatchi E, Rodier G, Sardet C, Le Cam LO Abstract The multifunctional E4F1 protein was originally identified as a cellular target of the E1A adenoviral oncoprotein. Although E4F1 is implicated in several key oncogenic pathways, its roles in tumorigenesis remain unclear. Using a genetically engineered mouse model of myeloid leukemia (histiocytic sarcomas, HS) based on the genetic inactivation of the tumor suppressor Ink4a/Arf locus, we have recently unraveled an unsuspected function of E4F1 in the survival of leukemic cells. In vivo, genetic ablation of E4F1 in established myeloid tumors results in tumor regression. E4F1 inactivation results in a cascade of alterations originating from dysfunctional mitochondria that induce increased reactive oxygen species (ROS) levels and ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361317 Mon, 31 Oct 2011 21:21:52 +0100 5361317 http://www.medworm.com/index.php?rid=5361316&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024747%26dopt%3DAbstract Authors: Mao K, Klionsky DJ Abstract The autophagy-dependent selective degradation of mitochondria (mitophagy) plays an important role in removing excessive, damaged and dysfunctional mitochondria to maintain a proper cellular homeostasis. Relative to its significance in cell physiology, very little is known about the molecular machinery and regulatory mechanism of mitophagy in mammalian cells or yeast. We found that two mitogen-activated protein kinases (MAPKs), Slt2 and Hog1, are required for mitophagy in Saccharomyces cerevisiae. Slt2 is involved in both mitophagy and pexophagy (the selective degradation of peroxisomes through autophagy), whereas Hog1 functions specifically in mitophagy. PMID: 22024747 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5361316 Mon, 31 Oct 2011 21:21:42 +0100 5361316 http://www.medworm.com/index.php?rid=5361315&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024748%26dopt%3DAbstract Authors: Lee S, Sato Y, Nixon RA Abstract Abnormally swollen regions of axons and dendrites (neurites) filled mainly with autophagy-related organelles represent the highly characteristic and widespread form of "neuritic dystrophy" in Alzheimer disease (AD), which implies dysfunction of autophagy and axonal transport. In this punctum, we discuss our recent findings that autophagic/lysosomal degradation is critical to proper axonal transport of autophagic vacuoles (AVs) and lysosomes. We showed that lysosomal protease inhibition induces defective axonal transport of specific cargoes, causing these cargoes to accumulate in axonal swellings that biochemically and morphologically resemble the dystrophic neurites in AD. Our findings suggest that a cargo-specific failure of axonal transpo... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361315 Mon, 31 Oct 2011 21:21:33 +0100 5361315 http://www.medworm.com/index.php?rid=5361314&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024749%26dopt%3DAbstract Authors: Mitsuhashi S, Nishino I Abstract Mitophagy, selective autophagy of mitochondria, has been extensively demonstrated in cultured cell models but has never been described in skeletal muscle in the context of muscle disease. We recently reported the first example of human muscle disease where mitophagy plays a role in the peculiar muscle pathology. This disease is caused by loss-of-function mutations in the CHKB gene encoding choline kinase beta. "Patients" and rostrocaudal muscular dystrophy (rmd) mice, spontaneous Chkb mutants, develop congenital muscular dystrophy with a peculiar mitochondrial abnormality-mitochondria are markedly enlarged at the periphery of muscle fibers and absent from the center. Choline kinase is the first enzymatic step in a biosynthetic pathway for p... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361314 Mon, 31 Oct 2011 21:21:23 +0100 5361314 http://www.medworm.com/index.php?rid=5361313&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024750%26dopt%3DAbstract Authors: King JS, Veltman DM, Insall RH Abstract The ability to respond and adapt to changes in the physical environment is a universal and essential cellular property. Here we demonstrate that cells respond to mechanical compressive stress by rapidly inducing autophagosome formation. We measure this response in both Dictyostelium and mammalian cells, indicating that this is an evolutionarily conserved, general response to mechanical stress. In Dictyostelium, the number of autophagosomes increases 20 fold within 10 minutes of 1kPa pressure being applied and a similar response is seen in mammalian cells after 30 minutes. We show in both cell types that autophagy is highly sensitive to changes in mechanical pressure and the response is graduated, with a half-maximal responses at ~0.2... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361313 Mon, 31 Oct 2011 21:21:14 +0100 5361313 http://www.medworm.com/index.php?rid=5361312&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024751%26dopt%3DAbstract Authors: Zhang Y, Yang JW, Ren X, Yang JM Abstract Our recent study revealed a new role of nucleus accumbens-1 (NAC1), a transcription factor belonging to the BTB/POZ gene family, in regulating autophagy. Moreover, we found that the high-mobility group box 1 (HMGB1), a chromatin-associated nuclear protein acting as an extracellular damage associated molecular pattern molecule (DAMP), is the downstream executor of NAC1 in modulating autophagy. In response to stress such as therapeutic insults, NAC1 increases the expression, cytosolic translocation and release of HMGB1; elevated level of the cytoplasmic HMGB1 leads to activation of autophagy. The NAC1-HMGB1 partnership may represent a previously unrecognized pathway that regulates autophagy in response to various stresses such as che... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361312 Mon, 31 Oct 2011 21:21:04 +0100 5361312 http://www.medworm.com/index.php?rid=5361311&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024752%26dopt%3DAbstract Authors: Grumati P, Coletto L, Schiavinato A, Castagnaro S, Bertaggia E, Sandri M, Bonaldo P Abstract Autophagy is a catabolic process that provides the degradation of altered/damaged organelles through the fusion between autophagosomes and lysosomes. Proper regulation of the autophagic flux is fundamental for the homeostasis of skeletal muscles in physiological conditions and in response to stress. Defective as well as excessive autophagy is detrimental for muscle health and has a pathogenic role in several forms of muscle diseases. Recently, we found that defective activation of the autophagic machinery plays a key role in the pathogenesis of muscular dystrophies linked to collagen VI. Impairment of the autophagic flux in collagen VI null (Col6a1 (-/-) ) mice causes accumulation ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361311 Mon, 31 Oct 2011 21:20:54 +0100 5361311 http://www.medworm.com/index.php?rid=5361310&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024753%26dopt%3DAbstract In this study we investigated the possible interaction between vaccinia virus and the autophagy membrane biogenesis machinery. Massive LC3 lipidation was observed in mouse fibroblast cells upon vaccinia virus infection. Surprisingly, the vaccinia virus induced LC3 lipidation was shown to be independent of ATG5 and ATG7, as the atg5 and atg7 null mouse embryonic fibroblasts (MEFs) exhibited the same high levels of LC3 lipidation as compared to the wild type MEFs. Mass spectrometry and immunoblotting analyses revealed that the viral infection led to the direct conjugation of ATG3, which is the E2-like enzyme required for LC3-phosphoethanonamine conjugation, to ATG12, which is a component of the E3-like ATG5-ATG12-ATG16 complex for LC3 lipidation. Consistently, ATG3 was shown to be required f... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361310 Mon, 31 Oct 2011 21:20:44 +0100 5361310 http://www.medworm.com/index.php?rid=5361309&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024754%26dopt%3DAbstract Evolution of the "autophagamiR" Autophagy. 2011 Dec 1;7(12) Authors: Gundara JS, Robinson BG, Sidhu SB Abstract MicroRNAs (miRs) are increasingly important diagnostic and prognostic markers in cancer but have not been defined in medullary thyroid carcinoma (MTC). MiR microarray profiling was performed on 19 primary MTC tumors, validated with qPCR in 45 cases and correlated with clinical outcomes. MiRs-183 and 375 were overexpressed and miR-9* underexpressed in sporadic versus hereditary MTC (SMTC; HMTC). MiR-183 and 375 overexpression predicted lateral nodal metastases, residual disease, distant metastases and mortality. MiR-183 knockdown in an MTC cell line (TT cells) reduced cellular proliferation in association with elevated LC3B expression. This is suggestive of increas... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361309 Mon, 31 Oct 2011 21:20:34 +0100 5361309 http://www.medworm.com/index.php?rid=5361308&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024755%26dopt%3DAbstract Authors: Shtutman M, Roninson IB Abstract COPI, a coatomer protein complex of secretory vesicles, is involved in Golgi and endoplasmic reticulum traffic and in early endosome maturation. The loss of COPI results in the fragmentation of Golgi, accumulation of immature autophagosomes, inhibition of autophagy, and cell death. Since COPI is required by all cells, it would appear an unlikely target for cancer treatment. However, our recent function-based genomic screen unexpectedly identified a specific COPI subunit, ζ1, as a cancer-specific target. The existing cancer drugs kill only proliferating but not growth-arrested tumor cells, but the depletion of ζ1 induces cell death in both dividing and non-dividing tumor cells, while sparing normal cells. The mechanism of this remarkable t... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361308 Mon, 31 Oct 2011 21:20:24 +0100 5361308 http://www.medworm.com/index.php?rid=5361307&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024756%26dopt%3DAbstract Authors: Bass A, Sauer D, Klionsky DJ Abstract A central part of the core macroautophagy (hereafter autophagy) machinery includes the two ubiquitin-like (Ubl) conjugation systems that involve the Ubl proteins Atg8 and Atg12. Although the functions of these proteins have not been fully elucidated, they play critical roles in autophagosome formation. For example, Atg8 is involved in cargo recognition, and the amount of Atg8 in part determines the size of the autophagosome, whereas Atg12 is part of a trimer that may function as an E3 ligase to facilitate Atg8 conjugation to phosphatidylethanolamine and determine, in part, the site of the conjugation reaction. Thus, fully functional autophagy requires both the Atg8 and Atg12 conjugation systems. Dysfunctional autophagy is associated wi... Autophagy journals http://www.medworm.com/rss/comments.php?id=5361307 Mon, 31 Oct 2011 21:20:15 +0100 5361307 http://www.medworm.com/index.php?rid=5231573&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21921693%26dopt%3DAbstract Authors: Ganley IG, Wong PM, Jiang X Abstract A close relationship exists between autophagy and endocytosis with both sharing lysosomes as their common end-point. Autophagy even requires a functional endocytic pathway. The point at which the two pathways merge, i.e., fusion of autophagosomes and endosomes with lysosomes is poorly understood. Early work in yeast and more recent studies in mammalian cells suggested that conventional membrane trafficking pathways control the fusion of autophagosomes with lysosomes; Rab GTPases are required to recruit tethering proteins which in turn coordinate the SNARE family of proteins that directly drive membrane fusion. Some components required for endosomes to fuse with lysosomes are also shared by autophagosomes; both are thought to require the... Autophagy journals http://www.medworm.com/rss/comments.php?id=5231573 Mon, 19 Sep 2011 18:04:39 +0100 5231573 http://www.medworm.com/index.php?rid=5231572&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21921694%26dopt%3DAbstract Authors: Van Humbeeck C, Cornelissen T, Vandenberghe W Abstract Mutations in the gene for the E3 ubiquitin ligase Parkin are the most prevalent cause of autosomal recessive Parkinson disease (PD), an incurable neurodegenerative disorder. Parkin surveys mitochondrial quality by translocating to depolarized mitochondria and inducing their selective macroautophagic removal (mitophagy). We recently reported that Parkin interacts with Ambra1 (activating molecule in Beclin 1-regulated autophagy), a protein that promotes autophagy in the vertebrate central nervous system. We discovered that prolonged mitochondrial depolarization strongly increases the interaction of Parkin with Ambra1. Ambra1 is recruited in a Parkin-dependent manner to perinuclear clusters of depolarized mitochondria, ac... Autophagy journals http://www.medworm.com/rss/comments.php?id=5231572 Mon, 19 Sep 2011 18:04:21 +0100 5231572 http://www.medworm.com/index.php?rid=5157446&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862879%26dopt%3DAbstract In this study, we sought to examine the specificity of three antibodies targeted against different peptide sequences within GABARAPL1: CHEM-CENT (an antibody raised against a short peptide sequence within the center of the protein), PTG-NTER (an antibody raised against the N-terminus of the protein) and PTG-FL (an antibody raised against the full-length protein). The results described in this article demonstrate the importance of testing antibody specificity under the conditions for which it will be used experimentally, a caution that should be taken when studying the expression of the GABARAP family proteins. PMID: 21862879 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5157446 Thu, 25 Aug 2011 22:16:08 +0100 5157446 http://www.medworm.com/index.php?rid=5103886&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21785263%26dopt%3DAbstract Authors: Settembre C, Ballabio A Autophagy is a fundamental catabolic process that plays a central role in health and disease. An efficient autophagic process relies on the cooperation of two distinct types of organelles: the autophagosome and the lysosome. We have identified a gene network that regulates the biogenesis and function of both organelles. Our findings reveal an important role of transcription in the regulation of starvation-induced autophagy, and link lysosomal biogenesis to autophagy. PMID: 21785263 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5103886 Sun, 07 Aug 2011 17:20:11 +0100 5103886 http://www.medworm.com/index.php?rid=5103885&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21795849%26dopt%3DAbstract Authors: Jung CH, Seo M, Otto NM, Kim DH ULK1 (Unc51-like kinase, hATG1) is a Ser/Thr kinase that plays a key role in inducing autophagy in response to starvation. ULK1 is phosphorylated and negatively regulated by the mammalian target of rapamycin complex 1 (mTORC1). Previous studies have shown that ULK1 is not only a downstream effector of mTORC1 but also a negative regulator of mTORC1 signaling. ( 1-3) Here, we investigated how ULK1 regulates mTORC1 signaling, and found that ULK1 inhibits the kinase activity of mTORC1 and cell proliferation. Deficiency or knockdown of ULK1 or its homolog ULK2 enhanced mTORC1 signaling, cell proliferation rates and accumulation of cell mass, whereas overexpression of ULK1 had the opposite effect. Knockdown of Atg13, the binding partner of ULK1 and UL... Autophagy journals http://www.medworm.com/rss/comments.php?id=5103885 Sun, 07 Aug 2011 17:19:52 +0100 5103885 http://www.medworm.com/index.php?rid=5103884&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21795850%26dopt%3DAbstract Authors: Ogawa M, Sasakawa C Bacterial intrusion of host cells can be recognized by the innate immune system, including autophagy, via multiple cellular pathways. We have identified Tecpr1 as an Atg5-binding partner, and found that Tecpr1 interacts with the Atg12-Atg5-Atg16L1 complex via binding to Atg5. In Shigella infected cells, Tecpr1 colocalizes with Atg5 and LC3 at Shigella-containing phagophores. Tecpr1 activity is required for efficient autophagy to target bacteria, but a deficiency of Tecpr1 in host cells does not have a marked effect on canonical autophagy. Tecpr1 plays an important role in promoting selective autophagy via the WIPI-2-Tecpr1-Atg5 pathway in targeting bacteria, protein aggregates and damaged mitochondria. PMID: 21795850 [PubMed - as supplied by publisher] ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5103884 Sun, 07 Aug 2011 17:19:36 +0100 5103884 http://www.medworm.com/index.php?rid=5103883&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21795851%26dopt%3DAbstract This study demonstrates that tyrosine deficiency causes mTORC1 inactivation and subsequent activation of autophagic pathway in Spr (-/-) mice. Therapeutic tyrosine diet completely rescued dwarfism and mTORC1 inhibition but inactivated autophagic pathway in Spr (-/-) mice. Tyrosine-dependent inactivation of mTORC1 was further supported by mTORC1 inactivation in Pah (enu2) mouse model lacking phenylalanine hydroxylase (Pah). NIH3T3 cells grown under the condition of tyrosine restriction exhibited autophagy induction. However, mTORC1 activation by RhebQ64L, a positive regulator of mTORC1, inactivated autophagic pathway in NIH3T3 cells under tyrosine-deficient conditions. In addition, this study first documents mTORC1 inactivation and autophagy induction in PKU patients with BH 4 deficiency. ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5103883 Sun, 07 Aug 2011 17:19:24 +0100 5103883 http://www.medworm.com/index.php?rid=5103882&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21795860%26dopt%3DAbstract Authors: Gabriely G, Teplyuk NM, Krichevsky AM Single microRNA (miRNA) can regulate expression of several or multiple principal targets in a specific microenvironment. In different cellular contexts, the same miRNA may exhibit diverse functions, depending on the repertoire and stoichiometry of its direct mRNA targets. For instance, in breast cancer, microRNA-10b (miR-10b) promotes invasion and metastasis of tumor cells through post-transcriptional regulation of HOXD10. In contrast, in glioblastoma (GBM), the most common and malignant primary brain tumor, miR-10b promotes proliferation and prevents death of cancer cells by targeting cell cycle inhibitors and pro-apoptotic genes. Here, we discuss a unique role of miR-10b in cancer cell survival, in diverse tumor microenvironments. PM... Autophagy journals http://www.medworm.com/rss/comments.php?id=5103882 Sun, 07 Aug 2011 17:19:04 +0100 5103882 http://www.medworm.com/index.php?rid=5103881&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21799305%26dopt%3DAbstract Authors: Cottam EM, Maier HJ, Manifava M, Vaux LC, Chandra-Schoenfelder P, Gerner W, Britton P, Ktistakis NT, Wileman T Autophagy is a cellular response to starvation which generates autophagosomes to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy can provide an innate defence against virus infection, or conversely autophagosomes can promote infection by facilitating assembly of replicase proteins. We demonstrate that the avian coronavirus, Infectious Bronchitis Virus (IBV) activates autophagy. A screen of individual IBV non-structural proteins (nsps) showed that autophagy was activated by IBV nsp6. This property was shared with nsp6 of mammalian coronaviruses Mouse Hepatitis Virus, and Severe Acute Respiratory Syndrome Vir... Autophagy journals http://www.medworm.com/rss/comments.php?id=5103881 Sun, 07 Aug 2011 17:18:43 +0100 5103881 http://www.medworm.com/index.php?rid=5103880&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21799306%26dopt%3DAbstract Authors: Young AR, Narita M, Narita M Evidence for a connection between lysosomes and mTOR is emerging. Seminal work from the Sabatini laboratory has shown that mTOR can be recruited to the lysosomal surface in response to amino acids, in a Rag GTPase-dependent manner, to become activated by Rheb. However the biological significance of this is not fully understood. Recent work from our laboratory has shown that lysosomes spatially link mTOR and autophagy forming a cytoplasmic compartment in close proximity to the Golgi apparatus (GA) during oncogenic Ras-induced senescence. The TOR-autophagy spatial coupling compartment (TASCC) is enriched for autolysosomes, but largely excludes autophagosomes. Our data suggest that mTOR, which is a positive regulator of protein synthesis, is recruited... Autophagy journals http://www.medworm.com/rss/comments.php?id=5103880 Sun, 07 Aug 2011 17:18:29 +0100 5103880 http://www.medworm.com/index.php?rid=5103879&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21804352%26dopt%3DAbstract Authors: Dokudovskaya S, Rout MP We now seem to live in a small world, in which everyone is highly interconnected. Cells, too, often also display tremendous interconnectivities in their component systems. As a recent case in point, we have identified a conserved protein complex-the SEA complex-that links the nuclear pore complex (NPC), the COPII vesicle coating complex, vacuoles and autophagy. In this punctum we will discuss the properties of this novel complex. PMID: 21804352 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5103879 Sun, 07 Aug 2011 17:18:11 +0100 5103879 http://www.medworm.com/index.php?rid=5103878&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21808150%26dopt%3DAbstract We report here that the Drosophila cyclin-dependent kinase PITSLRE is a modulator of autophagy. Loss of the human PITSLRE orthologue, CDK11, initially appears to induce autophagy, but at later time points CDK11 is critically required for autophagic flux and cargo digestion. Since PITSLRE/CDK11 regulates autophagy in both Drosophila and human cells, this kinase represents a novel phylogenetically conserved component of the autophagy machinery. PMID: 21808150 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5103878 Sun, 07 Aug 2011 17:17:45 +0100 5103878 http://www.medworm.com/index.php?rid=5103877&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21808151%26dopt%3DAbstract In this study, we utilized the TSC2 (-/-) mouse embryonic fibroblasts (MEFs) to study the involvement of autophagy in the enhanced susceptibility of TSC2-null cells to cell death. We first confirmed that both TSC1-null and TSC2-null MEFs are more sensitive to apoptosis in response to amino acid starvation (EBSS) and hypoxia. Second, we found that both the basal and inducible autophagy in TSC2 (-/-) MEFs is impaired, mainly due to constitutive activation of mTORC1. Third, suppression of autophagy by chloroquine and Atg7 knockdown sensitizes TSC2 (+/+) cells, but not TSC2 (-/-) cells, to EBSS-induced cell death. Conversely, the inhibition of mTORC1 by raptor knockdown and rapamycin activates autophagy and subsequently rescues TSC2 (-/-) cells. Finally, in starved cells, nutrients supplementa... Autophagy journals http://www.medworm.com/rss/comments.php?id=5103877 Sun, 07 Aug 2011 17:17:25 +0100 5103877 http://www.medworm.com/index.php?rid=5103876&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21811093%26dopt%3DAbstract Authors: Jing K, Song KS, Shin S, Kim N, Jeong S, Oh HR, Park JH, Seo KS, Heo JY, Han J, Park JI, Han C, Wu T, Kweon GR, Park SK, Yoon WH, Hwang BD, Lim K Docosahexaenoic acid (DHA) has been reported to induce tumor cell death by apoptosis. However, little is known about the effects of DHA on autophagy, another complex well-programmed process characterized by the sequestration of cytoplasmic material within autophagosomes. Here, we show that DHA increased both the level of microtubule-associated protein light-chain 3 and the number of autophagic vacuoles without impairing autophagic vesicle turnover, indicating that DHA induces not only apoptosis but also autophagy. We also observed that DHA-induced autophagy was accompanied by p53 loss. Inhibition of p53 increased DHA-induced autophag... Autophagy journals http://www.medworm.com/rss/comments.php?id=5103876 Sun, 07 Aug 2011 17:17:04 +0100 5103876 http://www.medworm.com/index.php?rid=5103875&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21814044%26dopt%3DAbstract Authors: Mellor KM, Reichelt ME, Delbridge LM The prominent occurrence of autophagy in fetal/neonatal myocardial tissue has been recognized for more than three decades as a key process in managing the period of perinatal nutrient deprivation. Fasting-induced autophagy has similarly been characterized as an expedient short-term cardiomyocyte response to nutrient restriction. Discerning how autophagy operates in the heart in disease contexts of substrate dysregulation is proving to be a much more complex challenge. Recent studies relating to insulin signaling and cardiac autophagy activation have provided new insights-and generated new contradictions. We highlight several anomalies and pose a number of questions, which emerge from these studies. How can myocardial autophagy induction be ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5103875 Sun, 07 Aug 2011 17:16:34 +0100 5103875 http://www.medworm.com/index.php?rid=5103874&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21814046%26dopt%3DAbstract Authors: Bareford MD, Hamed HA, Tang Y, Cruickshanks N, Burow ME, Fisher PB, Moran RG, Nephew KP, Grant S, Dent P Pemetrexed (ALIMTA) is a folate anti-metabolite that has been approved for the treatment of non-small cell lung cancer, and has been shown to stimulate autophagy. In the present study, we sought to further understand the role of autophagy in the response to pemetrexed and to test if combination therapy could enhance the level of toxicity through altered autophagy in tumor cells. The multi-kinase inhibitor sorafenib (NEXAVAR), used in the treatment of renal and hepatocellular carcinoma, suppresses tumor angiogenesis and promotes autophagy in tumor cells. We found that sorafenib interacted in a greater than additive fashion with pemetrexed to increase autophagy and to kill a ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5103874 Sun, 07 Aug 2011 17:16:02 +0100 5103874 http://www.medworm.com/index.php?rid=5057993&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21738011%26dopt%3DAbstract This study found that the BATS domain of Barkor targets the PtdIns3KC3 complex to early autophagic structures and senses highly curved membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(3)P). Consequently, this study uncovered an exciting new role for the PtdIns3KC3 complex as a potential inducer of autophagosome formation. Why is membrane curvature important? PMID: 21738011 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5057993 Sun, 24 Jul 2011 09:45:41 +0100 5057993 http://www.medworm.com/index.php?rid=5057992&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21738012%26dopt%3DAbstract We report here that autophagy triggered by oncogenic K-Ras mediates functional loss of mitochondria during cell transformation to overcome an energy deficit resulting from glucose deficiency. When Rat2 cells were infected with a retrovirus harboring constitutively active K-Ras (V12) , mitochondrial respiration significantly declined in parallel with the acquisition of transformation characteristics. Decreased respiration was not related to mitochondrial biogenesis but was inversely associated with the increased formation of acidic vesicles enclosing mitochondria, during which autophagy-related proteins such as Beclin 1, Atg5, LC3-II, and vacuolar ATPases were induced. Interestingly, blocking autophagy with conventional inhibitors (bafilomycin A, 3-methyladenin) and siRNA-mediated knockdown... Autophagy journals http://www.medworm.com/rss/comments.php?id=5057992 Sun, 24 Jul 2011 09:45:36 +0100 5057992 http://www.medworm.com/index.php?rid=5057991&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743300%26dopt%3DAbstract Authors: Gomes LC, Scorrano L Mitochondrial morphological and structural changes play a role in several cellular processes, including apoptosis. We recently reported that mitochondrial elongation is also critical to sustain cell viability during macroautophagy. During macroautophagy unopposed mitochondrial fusion leads to organelle elongation both in vitro and in vivo. Longer mitochondria are protected from being degraded and possess more cristae where activity of the ATP synthase is increased, optimizing ATP production in times of nutrient restriction. PMID: 21743300 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=5057991 Sun, 24 Jul 2011 09:45:32 +0100 5057991 http://www.medworm.com/index.php?rid=5057990&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21750416%26dopt%3DAbstract Authors: Ugland H, Naderi S, Brech A, Collas P, Blomhoff HK Autophagy plays an important role in cellular remodelling during differentiation and development, however little is known about its regulation in stem cells. Here we show that cAMP, a well-known differentiation factor for mesenchymal stem cells (MSCs), is also a potent inducer of autophagy in these cells. We have previously shown that activation of the cAMP-signaling pathway inhibits proliferation of MSCs despite induction of the cell cycle component cyclin E. Here, we demonstrate a critical role of cyclin E in the induction of autophagy. Our data suggest a model in which cAMP-signaling via ERK-mediated induction of cyclin E leads to enhanced perinuclear recruitment of Beclin 1 and formation of autophagosomes. Given the roles ... Autophagy journals http://www.medworm.com/rss/comments.php?id=5057990 Sun, 24 Jul 2011 09:45:27 +0100 5057990 http://www.medworm.com/index.php?rid=4961602&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21654208%26dopt%3DAbstract Authors: Dong LW, Hou YJ, Tan YX, Tang L, Pan YF, Wang M, Wang HY Autophagy enables cells to recycle long-lived proteins or damaged organelles. Beclin 1 plays important roles in autophagy, differentiation, apoptosis and the development and progression of cancer, but the expression of Beclin 1 and its possible role in primary intrahepatic cholangiocarcinoma (ICC) has not been reported yet. The study aimed to investigate Beclin 1 expression and its prognostic significance in ICC. Firstly, we assessed the expression levels of Beclin 1 by real-time PCR in fifty ICC samples and found beclin1 mRNA expression was markedly increased in 78% (39 of 50) samples compared with normal bile duct epithelium. Beclin 1 protein expression in 108 tumor specimens from patients diagnosed with ICC was examin... Autophagy journals http://www.medworm.com/rss/comments.php?id=4961602 Fri, 24 Jun 2011 09:15:55 +0100 4961602 http://www.medworm.com/index.php?rid=4961601&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21670587%26dopt%3DAbstract In conclusion, Joka2, and presumably the process of selective autophagy, might constitute an important part of plant response to environmental stresses. PMID: 21670587 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4961601 Fri, 24 Jun 2011 09:15:44 +0100 4961601 http://www.medworm.com/index.php?rid=4961600&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21673516%26dopt%3DAbstract Authors: Huang Y, Hou JK, Chen TT, Zhao XY, Yan ZW, Zhang J, Yang J, Kogan SC, Chen GQ Autophagy is a highly conserved, closely regulated homeostatic cellular activity that allows for the bulk degradation of long-lived proteins and cytoplasmic organelles. Its roles in cancer initiation and progression and in determining the response of tumor cells to anticancer therapy are complicated, and only limited investigation has been conducted on the potential significance of autophagy in the pathogenesis and therapeutic response of acute myeloid leukemia. Here we demonstrate that the inducible or transfected expression of the acute promyelocytic leukemia (APL)-specific PML-RARα, but not PLZF-RARα or NPM-RARα, fusion protein upregulates constitutive autophagy activation in leukemic and nonle... Autophagy journals http://www.medworm.com/rss/comments.php?id=4961600 Fri, 24 Jun 2011 09:15:31 +0100 4961600 http://www.medworm.com/index.php?rid=4961599&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21673517%26dopt%3DAbstract Authors: Plantinga TS, Joosten LA, Netea MG In recent years considerable advances in understanding the pathogenesis of Crohn disease have been achieved, with the identification of susceptibility variants of genes that are part of the autophagy machinery, i.e., ATG16L1 and IRGM. Subsequent functional studies have been conducted to unravel the underlying mechanism of this genetic association. For the ATG16L1 Thr300Ala polymorphism (c.898A>G, rs2241880), it was demonstrated that the risk variant is associated with a reduced capacity of innate immune cells to induce autophagy upon triggering with specific microbial structures such as peptidoglycans, that are specifically recognized by the intracellular pattern-recognition receptor nucleotide oligomerization domain-2 (NOD2). Due to the i... Autophagy journals http://www.medworm.com/rss/comments.php?id=4961599 Fri, 24 Jun 2011 09:15:27 +0100 4961599 http://www.medworm.com/index.php?rid=4961598&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21677510%26dopt%3DAbstract Authors: Pattison JS, Robbins J Increasing evidence suggests that misfolded proteins and intracellular aggregates contribute to cardiac disease and heart failure. We wished to determine if autophagic induction by Atg7 is sufficient to reduce misfolded protein and aggregate content in protein misfolding-stressed cardiomyocytes. We used loss- and gain-of-function approaches in cultured cardiomyocytes to determine the effects of ATG7 knockdown and Atg7 overexpression in protein conformation-based toxicity induced by expression of a mutant aB crystallin (CryAB (R120G) ) known to cause human heart disease. We show that Atg7 induces basal autophagy and rescues the CryAB accumulation of misfolded proteins and aggregates in cardiomyocytes. PMID: 21677510 [PubMed - as supplied by publisher]... Autophagy journals http://www.medworm.com/rss/comments.php?id=4961598 Fri, 24 Jun 2011 09:15:23 +0100 4961598 http://www.medworm.com/index.php?rid=4961597&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21685727%26dopt%3DAbstract Authors: Xie Z, He C, Zou MH We have recently shown that in diabetic OVE26 mice (type I diabetes), the AMP-activated protein kinase (AMPK) is reduced along with cardiac dysfunction and decreased cardiac autophagy. Genetic inhibition of AMPK in cardiomyocytes attenuates cardiac autophagy, exacerbates cardiac dysfunction, and increases mortality in diabetic mice. More importantly, we have found chronic AMPK activation with metformin, one of the most used anti-diabetic drugs and a well characterized AMPK activator, significantly enhances autophagic activity, preserves cardiac function, and prevents most of the primary characteristics of diabetic cardiomyopathy in OVE26 mice, but not in dominant negative-AMPK diabetic mice. We conclude that AMPK activation protects cardiac structure and fu... Autophagy journals http://www.medworm.com/rss/comments.php?id=4961597 Fri, 24 Jun 2011 09:15:19 +0100 4961597 http://www.medworm.com/index.php?rid=4961596&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691146%26dopt%3DAbstract Authors: Kang R, Livesey KM, Zeh HJ, Loze MT, Tang D Autophagy is a dynamic process for degradation of cytosolic components such as dysfunctional organelles and proteins and a means for generating metabolic substrates during periods of starvation. Mitochondrial autophagy ("mitophagy") is a selective form of autophagy, which is important in maintaining mitochondrial homeostasis. High mobility group box 1 (HMGB1) plays important intranuclear, cytosolic, and extracellular roles in the regulation of autophagy. Cytoplasmic HMGB1 is a novel Beclin 1-binding protein active in autophagy. Extracellular HMGB1 induces autophagy, and this role is dependent on its redox state and receptor (Receptor for Advanced Glycation End products, RAGE) expression. Nuclear HMGB1 modulates the expression of heat... Autophagy journals http://www.medworm.com/rss/comments.php?id=4961596 Fri, 24 Jun 2011 09:15:15 +0100 4961596 http://www.medworm.com/index.php?rid=4961595&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691147%26dopt%3DAbstract Authors: Shi YH, Ding ZB, Zhou J, Hui B, Shi GM, Ke AW, Wang XY, Dai Z, Peng YF, Gu CY, Qiu SJ, Fan J Sorafenib, a potent multi-kinase inhibitor, has been recognized as the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC). However, the direct functional mechanism of tumor lethality mediated by sorafenib remains to be fully characterized, and the precise mechanism of drug resistance are largely unknown. Here, we showed sorafenib induced both apoptosis and autophagy in human HCC cells through a mechanism that involved endoplasmic reticulum (ER) stress and was independent of the MEK1/2-ERK1/2 pathway. Up-regulation of IRE1 signals from sorafenib-induced ER stress was critical for the induction of autophagy. Moreover, autophagy activation alleviated the... Autophagy journals http://www.medworm.com/rss/comments.php?id=4961595 Fri, 24 Jun 2011 09:15:12 +0100 4961595 http://www.medworm.com/index.php?rid=4961594&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691148%26dopt%3DAbstract Authors: Trocoli A, Mathieu J, Priault M, Reiffers J, Souquère S, Pierron G, Besançon F, Djavaheri-Mergny M Acute promyelocytic leukemia (APL) results from a blockade of granulocyte differentiation at the promyelocytic stage. All-trans retinoic acid (ATRA) has been shown to induce clinical remission in APL patients by enhancing the rapid differentiation of APL cells and the clearance of PML-RAR alpha, APL's hallmark oncoprotein. In the present study, we demonstrate that both autophagy and Beclin 1, an autophagic protein, are upregulated during the course of ATRA-induced neutrophil/granulocyte differentiation of an APL-derived cell line named NB4 cells. This induction of autophagy is associated with downregulation of Bcl-2 and inhibition of mTOR activity. Small interfering RNA-mediate... Autophagy journals http://www.medworm.com/rss/comments.php?id=4961594 Fri, 24 Jun 2011 09:15:07 +0100 4961594 http://www.medworm.com/index.php?rid=4912741&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21642768%26dopt%3DAbstract Authors: Zschocke J, Rein T The prevailing view of antidepressants' (ADs) mode of action primarily focuses on their impact on neurotransmitter circuits, since the corresponding transporters and receptors are common targets of ADs. However, mounting evidence points to additional target structures, which may either support the beneficial effects or account for undesired side-effects of ADs. Recently, we analyzed the influence of three ADs of different classes on autophagy-related processes in primary astrocytes and neurons. While amitriptyline (AMI) and citalopram (CIT) upregulates the expression of autophagic markers such as LC3B-II or Beclin 1, venlafaxine fails to exert these effects. Autophagy triggered by AMI and CIT is functional in terms of autophagic flux, and is partially mediat... Autophagy journals http://www.medworm.com/rss/comments.php?id=4912741 Fri, 10 Jun 2011 11:54:17 +0100 4912741 http://www.medworm.com/index.php?rid=4912707&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21646862%26dopt%3DAbstract In conclusion, Beclin 1-independent autophagy is an important contributor to both the caspase-dependent and -independent components of neuronal apoptosis and may be considered as an important therapeutic target in neural conditions involving apoptosis. PMID: 21646862 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4912707 Fri, 10 Jun 2011 09:11:44 +0100 4912707 http://www.medworm.com/index.php?rid=4912696&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21646864%26dopt%3DAbstract Authors: Sun WL, Chen J, Wang YP, Zheng H Epirubicin (EPI) is one of the most effective drugs against cancer. But the acquired resistance of cancer cells to EPI is becoming a major obstacle for successful cancer therapy. Recently, some studies have revealed that macroautophagy (here referred to as autophagy) may protect the cancer cell from anti-cancer drug-induced death, so autophagy might be related to the development of drug-resistance to these reagents. However, the relationship between autophagy and drug-resistance has yet to be defined. Our study showed that EPI induced autophagy in human breast cancer MCF-7 cells. And the EPI-induced autophagy protected MCF-7 cells from EPI-induced apoptosis. Furthermore, autophagy was elevated in EPI-resistant MCF-7 cells (MCF-7er cells), and i... Autophagy journals http://www.medworm.com/rss/comments.php?id=4912696 Fri, 10 Jun 2011 07:49:54 +0100 4912696 http://www.medworm.com/index.php?rid=4865906&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21566462%26dopt%3DAbstract Authors: Eskelinen EL, Reggiori F, Baba M, Kovács AL, Seglen PO Autophagy was first discovered by transmission electron microscopy more than 50 years ago. For decades, electron microscopy was the only way to reliably detect autophagic compartments in cells because no specific protein markers were known. In the 1970s, however, the introduction of biochemical methods enabled quantitative studies of autophagic-lysosomal degradation, and in the 1980s specific biochemical assays for autophagic sequestration became available. Since the identification of autophagy-related genes in the 1990s, combined fluorescence microscopy, biochemical and genetic methods have taken the leading role in autophagy research. However, electron microscopy is still needed to confirm and verify results obtained by... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865906 Fri, 27 May 2011 02:01:27 +0100 4865906 http://www.medworm.com/index.php?rid=4865905&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21593591%26dopt%3DAbstract Authors: Lorente M, Torres S, Salazar M, Carracedo A, Hernández-Tiedra S, Rodríguez-Fornés F, García-Taboada E, Meléndez B, Mollejo M, Campos-Martín Y, Barcia JA, Guzmán M, Velasco G Δ ( 9) -tetrahydrocannabinol (THC), the main active component of marijuana, promotes cancer cell death via autophagy stimulation. We find that activation of the tyrosine kinase receptor ALK by its ligand midkine interferes with the signaling mechanism by which THC promotes autophagy-mediated glioma cell death. PMID: 21593591 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4865905 Fri, 27 May 2011 02:01:21 +0100 4865905 http://www.medworm.com/index.php?rid=4865904&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21593592%26dopt%3DAbstract Authors: Cao DJ, Hill JA The heart is a highly plastic organ. In a recent study, we found that autophagy is a required element in load-induced cardiomyocyte growth; when autophagy is suppressed, the heart does not grow. Conversely, afterload stress triggers a transient increase in cardiomyocyte autophagic activity which settles to a new-higher-baseline once the heart has re-achieved steady-state size. Our work went on to decipher the role of histone deacetylases in this biology. PMID: 21593592 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4865904 Fri, 27 May 2011 02:01:17 +0100 4865904 http://www.medworm.com/index.php?rid=4865903&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21597319%26dopt%3DAbstract Authors: Le Grand JN, Chakrama FZ, Seguin-Py S, Fraichard A, Delage-Mourroux R, Jouvenot M, Boyer-Guittaut M The GABARAPL1 (GABARAP-LIKE 1) gene was first described as an early estrogen-regulated gene that shares a high sequence homology with GABARAP and is thus a part of the GABARAP family. GABARAPL1, like GABARAP, interacts with the GABAA receptor and tubulin and promotes tubulin polymerization. The GABARAP family members (GABARAP, GABARAPL1 and GABARAPL2) and their close homologs (LC3 and Atg8) are not only involved in the transport of proteins or vesicles but are also implicated in various mechanisms such as autophagy, cell death, cell proliferation and tumor progression. However, despite these similarities, GABARAPL1 displays a complex regulation that is different from that of oth... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865903 Fri, 27 May 2011 02:01:12 +0100 4865903 http://www.medworm.com/index.php?rid=4865902&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21597320%26dopt%3DAbstract Authors: Itoh T, Fukuda M Atg8 and its homologs are essential for autophagosome formation in various species. In animal cells, Atg8 homologs have an additional function in clearance of damaged organelles and bacteria, acting as a landmark for selective autophagy. We have recently shown that OATL1, a Rab-GTPase-activating protein (Rab-GAP), is a novel binding partner of Atg8 homologs in mammalian cells, but to our surprise, it is not a substrate of autophagy. Further analysis indicates that OATL1 is involved in the fusion between autophagosomes and lysosomes through its GAP activity and its Atg8 homolog binding activity. Our findings suggest a novel function of Atg8 homologs as a scaffold for signal transduction that regulates autophagosomal maturation. PMID: 21597320 [PubMed - as s... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865902 Fri, 27 May 2011 02:01:08 +0100 4865902 http://www.medworm.com/index.php?rid=4865901&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21606679%26dopt%3DAbstract Authors: Yin X, Cao L, Peng Y, Tan Y, Xie M, Kang R, Livesey KM, Tang D Autophagy and apoptosis are tightly regulated biological processes that are crucial for cell growth, development and tissue homeostasis. UVRAG (UV radiation resistance-associated gene), a mammalian homolog of yeast Vps38, activates the Beclin 1/PtdIns3KC3 (class III phosphatidylinositol-3-kinase) complex, which promotes autophagosome formation. Moreover, UVRAG promotes autophagosome maturation by recruiting class C Vps complexes (HOPS complexes) and Rab7 of the late endosome. We found that UVRAG has anti-apoptotic activity during tumor therapy through interactions with Bax. UVRAG inhibits Bax translocation from the cytosol to mitochondria during chemotherapy- or UV irradiation-induced apoptosis of human tumor cells... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865901 Fri, 27 May 2011 02:01:03 +0100 4865901 http://www.medworm.com/index.php?rid=4865900&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21606680%26dopt%3DAbstract We report a novel method that enables high-throughput, high-content assessment of LC3 punctae and caspase-3 cleavage at the single cell level. PMID: 21606680 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4865900 Fri, 27 May 2011 02:00:59 +0100 4865900 http://www.medworm.com/index.php?rid=4865899&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21606681%26dopt%3DAbstract Authors: Ng A, Xavier RJ The leucine-rich repeats (LRR)-containing domain is evolutionarily conserved in many proteins associated with innate immunity in plants, invertebrates and vertebrates. Serving as a first line of defense, the innate immune response is initiated through the sensing of pathogen-associated molecular patterns (PAMPs). In plants, NBS (nucleotide-binding site)-LRR proteins provide recognition of pathogen products of avirulence (AVR) genes. LRRs also promote interaction between LRR proteins as observed in receptor-coreceptor complexes. In mammals, toll-like receptors (TLRs) and NOD-like receptors (NLRs) through their LRR domain, sense molecular determinants from a structurally diverse set of bacterial, fungal, parasite and viral-derived components. In humans, at least ... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865899 Fri, 27 May 2011 02:00:53 +0100 4865899 http://www.medworm.com/index.php?rid=4865898&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21606682%26dopt%3DAbstract Authors: Isaka Y, Kimura T, Takabatake Y In kidney, proximal tubules consume a large amount of energy in the process of electrolyte reabsorption. These tubules contain large quantities of mitochondria which provide the energy for this reabsorption. Proximal tubules are susceptible to many kinds of insults such as ischemia-reperfusion injury and nephrotoxic substrates, but little is known of the factors that counteract cellular stress signaling pathways. Autophagy mediates bulk degradation and recycling of cytoplasmic constituents to maintain cellular homeostasis. We demonstrated the critical role of autophagy in normal proximal tubule function and protection against acute tubular injury. PMID: 21606682 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4865898 Fri, 27 May 2011 02:00:47 +0100 4865898 http://www.medworm.com/index.php?rid=4865897&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21606683%26dopt%3DAbstract Authors: Shahnazari S, Namolovan A, Mogridge J, Kim PK, Brumell JH Autophagy plays a significant role in innate and adaptive immune responses to microbial infection. Some pathogenic bacteria have developed strategies to evade killing by host autophagy. These include the use of 'camouflage' proteins to block targeting to the autophagy pathway and the use of pore-forming toxins to block autophagosome maturation. However, general inhibition of host autophagy by bacterial pathogens has not been observed to date. Here we demonstrate that bacterial cAMP-elevating toxins from B. anthracis and V. cholera can inhibit host antimicrobial autophagy, including autophagic targeting of S. Typhimurium and latex bead phagosomes. Autophagy inhibition required the cAMP effector protein kinase A. Formatio... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865897 Fri, 27 May 2011 02:00:42 +0100 4865897 http://www.medworm.com/index.php?rid=4865896&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21606684%26dopt%3DAbstract Authors: Chou TF, Deshaies RJ Specific p97 inhibitors are valuable research tools to carry out mechanistic and cellular investigations of p97 biology. p97 is an abundant, ubiquitin-selective chaperone that has multiple functions and is essential for life. Therefore, genetic methods that require long incubations like siRNA or expression of dominant-negative p97 mutants are likely to generate complicated outcomes due to secondary consequences that arise upon slow depletion of p97 activity. We recently identified a small molecule p97 inhibitor, N ( 2) ,N ( 4) -dibenzylquinazoline-2,4-diamine (DBeQ), and documented its effects on blocking autophagic degradation of LC3-II and proteasomal degradation of a p97-dependent ubiquitin-proteasome system (UPS) substrate. What distinguishes DBeQ from... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865896 Fri, 27 May 2011 02:00:36 +0100 4865896 http://www.medworm.com/index.php?rid=4865895&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21606687%26dopt%3DAbstract Authors: Svenning S, Lamark T, Krause K, Johansen T (Macro)autophagy encompasses both an unselective, bulk degradation of cytoplasmic contents as well as selective autophagy of damaged organelles, intracellular microbes, protein aggregates, cellular structures and specific soluble proteins. Selective autophagy is mediated by autophagic adapters, like p62/SQSTM1 and NBR1. p62 and NBR1 are themselves selective autophagy substrates, but they also act as cargo receptors for degradation of other substrates. Surprisingly, we found that homologs of NBR1 are distributed throughout the eukaryotic kingdom, while p62 is confined to the metazoans. As a representative of all organisms having only an NBR1 homolog we studied Arabidopsis thaliana NBR1 (AtNBR1) in more detail. AtNBR1 is more similar to... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865895 Fri, 27 May 2011 02:00:31 +0100 4865895 http://www.medworm.com/index.php?rid=4865894&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21610315%26dopt%3DAbstract Authors: Li H, Wang P, Yu J, Zhang L Autophagy is often found in apoptosis-defective cancer cells and contributes to chemotherapy resistance. However, it is far from clear how the coordination of apoptosis and autophagy determines sensitivity of cancer cells to chemotherapy. Our recent study showed that Beclin 1, a key regulator of autophagy, is cleaved by caspase 8 at the execution stage of chemotherapy-induced and mitochondria-mediated apoptosis. Perturbation of Beclin 1 cleavage, by knock-in of a mutation, phenocopies the autophagy observed in apoptosis-defective cancer cells, and renders chemotherapy resistance in vitro and in vivo. These results demonstrate an important role of caspases in suppressing autophagy by cleaving autophagic machinery. PMID: 21610315 [PubMed - as supp... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865894 Fri, 27 May 2011 02:00:27 +0100 4865894 http://www.medworm.com/index.php?rid=4865893&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21610316%26dopt%3DAbstract In this study, we demonstrate that peptide-conjugated polymeric nanoparticles can be used to visualize Atg4 activity in both cell-free and cell culture systems. The fluorescence imaging of cells incubated with nanoparticles demonstrates that Atg4 activity is activated in the autophagy-induced conditions, but suppressed in the autophagy-inhibited conditions. These results indicate that Atg4 activity is correlated with autophagic flux through its own regulatory pathway. Therefore, our strategy provides an alternative detection method that can clearly distinguish between an "autophagy active" and "autophagy inactive" state in cultured cells. As our nanoparticles are highly cell-permeable and biocompatible, this detection system has general applicability to living cells and can be extended to ... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865893 Fri, 27 May 2011 02:00:21 +0100 4865893 http://www.medworm.com/index.php?rid=4865892&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21610319%26dopt%3DAbstract Authors: Overbye A, Sætre F, Hagen LK, Johansen HT, Seglen PO To investigate the stepwise autophagic-lysosomal processing of hepatocellular proteins, the abundant cytosolic enzyme, betaine:homocysteine methyltransferase (BHMT) was used as a probe. Full-length (45 kDa) endogenous BHMT was found to be cleaved in an autophagy-dependent (3-methyladenine-sensitive) manner in isolated rat hepatocytes to generate a novel N-terminal 10-kDa fragment (p10) identified and characterized by mass spectrometry. The cleavage site was consistent with cleavage by the asparaginyl proteinase, legumain, and indeed a specific inhibitor of this enzyme (AJN-230) was able to completely suppress p10 formation in intact cells, causing instead accumulation of a 42-kDa intermediate. To prevent further degradation... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865892 Fri, 27 May 2011 02:00:15 +0100 4865892 http://www.medworm.com/index.php?rid=4865891&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21610320%26dopt%3DAbstract In this study, we examined the biological activities of quercetin against gastric cancer. Our studies demonstrated that exposure of gastric cancer cells AGS and MKN28 to quercetin resulted in pronounced pro-apoptotic effect through activating the mitochondria pathway. Meanwhile, treatment with quercetin induced appearance of autophagic vacuoles, formation of acidic vesicular organelles (AVOs), conversion of LC3-I to LC3-II, recruitment of LC3-II to the autophagosomes as well as activation of autophagy genes, suggesting that quercetin initiates the autophagic progression in gastric cancer cells. Furthermore, either administration of autophagic inhibitor chloroquine or selective ablation of atg5 or beclin 1 using small interfering RNA (siRNA) could augment quercetin-induced apoptotic cell de... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865891 Fri, 27 May 2011 02:00:10 +0100 4865891 http://www.medworm.com/index.php?rid=4865890&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21610321%26dopt%3DAbstract Authors: Bhutia SK, Das SK, Azab B, Dash R, Su ZZ, Lee SG, Dent P, Curiel DT, Sarkar D, Fisher PB MDA-7/IL-24 has noteworthy potential as an anticancer therapeutic because of its diversity of antitumor properties, its lack of toxicity toward normal cells and tissues, and its safety and efficacy as evidenced in a phase I clinical trial. In a recent study, we document that Ad.mda-7-induced ER stress and ceramide production leads to early autophagy that subsequently switches to apoptosis in human prostate cancer cells. During the apoptotic phase, the MDA-7/IL-24 protein physically interacts with Beclin 1 and this interaction might inhibit Beclin 1 function culminating in apoptosis. Conversely, Ad.mda-7 infection leads to calpain-mediated cleavage of the ATG5 protein that might also facili... Autophagy journals http://www.medworm.com/rss/comments.php?id=4865890 Fri, 27 May 2011 02:00:06 +0100 4865890 http://www.medworm.com/index.php?rid=4813069&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21552009%26dopt%3DAbstract Authors: Mortensen M, Watson AS, Simon AK The regulated lysosomal degradation pathway of autophagy prevents cellular damage and thus protects from malignant transformation. Autophagy is also required for the maturation of various hematopoietic lineages, namely the erythroid and lymphoid ones, yet its role in adult hematopoietic stem cells (HSCs) remained unexplored. While normal HSCs sustain life-long hematopoiesis, malignant transformation of HSCs or early progenitors leads to leukemia. Mechanisms protecting HSCs from cellular damage are therefore essential to prevent hematopoietic malignancies. By conditionally deleting the essential autophagy gene Atg7 in the hematopoietic system, we found that autophagy is required for the maintenance of true HSCs and therefore also of downstream h... Autophagy journals http://www.medworm.com/rss/comments.php?id=4813069 Thu, 12 May 2011 11:15:11 +0100 4813069 http://www.medworm.com/index.php?rid=4813067&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21555918%26dopt%3DAbstract In this study, we examined the effects of mitochondrial photodamage catalyzed by low (≤ 1 µM) concentrations of the photosensitizing agent termed benzoporphyrin derivative (BPD, Verteporfin) on murine hepatoma 1c1c7 cells. Apoptosis was not observed until several hours after irradiation of photosensitized cells. Autophagy was clearly cytoprotective since PDT efficacy was significantly enhanced in a knockdown sub-line (KD) in which the level of a critical autophagy protein (Atg7) was markedly reduced. This result indicates that autophagy can protect from phototoxicity even when apoptosis is substantially delayed. Much higher concentrations (≥10 µM) of BPD had previously been shown to inhibit autophagosome formation. Phototoxicity studies carried out with 10 µM BPD and a proportionall... Autophagy journals http://www.medworm.com/rss/comments.php?id=4813067 Thu, 12 May 2011 11:15:07 +0100 4813067 http://www.medworm.com/index.php?rid=4582563&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21325880%26dopt%3DAbstract Authors: O'Donovan TR, O'Sullivan GC, McKenna S We investigated the cell-death mechanisms induced in esophageal cancer cells in response to the chemotherapeutic drugs, 5-fluorouracil (5-FU) and cisplatin. Chemo-sensitive cell lines exhibited apoptosis whereas chemo-resistant populations exhibited autophagy and a morphology resembling type II programmed cell death (PCD). Cell populations that respond with autophagy are more resistant and will recover following withdrawal of the chemotherapeutic agents. Specific inhibition of early autophagy induction with siRNA targeted to Beclin 1 and ATG7 significantly enhanced the effect of 5-FU and reduced the recovery of drug-treated cells. Pharmacological inhibitors of autophagy were evaluated for their ability to improve chemotherapeutic effect. ... Autophagy journals http://www.medworm.com/rss/comments.php?id=4582563 Tue, 15 Mar 2011 10:30:21 +0100 4582563 http://www.medworm.com/index.php?rid=4582562&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21325881%26dopt%3DAbstract In this study we show that detergent fractionation followed by Western analysis of insoluble ubiquitinated proteins (IUP), mammalian p62 and its Drosophila homologue, Ref(2)P can be used to quantitatively assess the activity level of aggregate clearance (aggrephagy) in complex tissues. Using this technique we show that genetic or age-dependent changes that modify the long-term enhancement or suppression of aggrephagy can be identified. Moreover, using the Drosophila model system this method can be used to establish autophagy-dependent protein clearance profiles that are occurring under a wide range of physiological conditions including developmental, fasting and altered metabolic pathways. This technique can also be used to examine proteopathies that are associated with human disorders suc... Autophagy journals http://www.medworm.com/rss/comments.php?id=4582562 Tue, 15 Mar 2011 10:30:18 +0100 4582562 http://www.medworm.com/index.php?rid=4582561&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21389787%26dopt%3DAbstract Authors: Klionsky DJ, Meijer AJ Now that many of the components of the autophagy machinery have been identified, in particular the autophagy-related (Atg) proteins, increasing focus is being directed toward the role of autophagy in health and disease. Accordingly, it is of ever-greater importance to understand the central role of autophagy in cellular metabolism, a point with which many people will likely agree. However, in our rush to understand autophagy's function in metabolism, we tend to overlook the role of metabolism in regulating autophagy, even though substantial work has been done on this topic. One of the pioneers in this area is Alfred "Fred" J. Meijer. PMID: 21389787 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4582561 Tue, 15 Mar 2011 10:30:14 +0100 4582561 http://www.medworm.com/index.php?rid=4474354&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21270513%26dopt%3DAbstract Authors: Gargini R, García-Escudero V, Izquierdo M Autophagy is mainly a cellular recycling process that promotes survival, but it can also cause cell death if cell injury persists. The role of mitophagy in tumorigenesis remains uncertain. Other cell death types, such as apoptosis or necrosis, are often altered during tumor development and therefore are not ideal targets to generate efficient antitumor therapies. We have used the system linamarase/linamarin/glucose oxidase (lis/lin/GO) to eliminate tumor cells. This therapeutic strategy is based on the combination of cyanide and oxidative stress to abrogate tumor growth. After severe mitochondrial insult by lis/lin/GO, the electron transport chain is blocked and hydrogen peroxide production increased. This triggers a degradative phase... Autophagy journals http://www.medworm.com/rss/comments.php?id=4474354 Tue, 15 Feb 2011 00:31:11 +0100 4474354 http://www.medworm.com/index.php?rid=4474352&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21270514%26dopt%3DAbstract Authors: Thorburn A Many people are studying how autophagy intersects with cell death. While most of those studies relate to autophagy acting as a protective mechanism (e.g., to block apoptosis), many papers conclude that autophagy is a death mechanism, and there is a widespread belief that autophagy (in most, but not all cases, we are talking about macroautophagy) can both kill and protect cells depending on the circumstances. Not surprisingly therefore, many of the papers submitted to Autophagy study the relationship between autophagy and cell death. PMID: 21270514 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4474352 Tue, 15 Feb 2011 00:31:03 +0100 4474352 http://www.medworm.com/index.php?rid=4474351&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21278489%26dopt%3DAbstract Authors: Meijer AJ, Klionsky DJ PMID: 21278489 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4474351 Tue, 15 Feb 2011 00:30:55 +0100 4474351 http://www.medworm.com/index.php?rid=4474350&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21282971%26dopt%3DAbstract Authors: Page N, Gros F, Schall N, Briand JP, Muller S The P140 phosphopeptide encompassing residues 131-151 of the spliceosomal U1-70K snRNP protein displays protective properties in lupus patients and MRL/lpr mice. It increases peripheral blood lymphocyte apoptosis via a mechanism involving γδ T cells. After intravenous administration, P140 accumulates in the lungs and spleen. It binds both the HSC70/Hsp73 chaperone and MHC class II (MHCII) molecules, which colocalize in splenic MRL/lpr B cells. Expression of HSC70 and MHCII, which is increased in MRL/lpr splenic B cells, is diminished after P140 administration. P140 impairs refolding properties of HSC70 and alters expression of stable MHCII molecules in B lymphocytes. In MRL/lpr B cells, P140 increases the accumulation of the auto... Autophagy journals http://www.medworm.com/rss/comments.php?id=4474350 Tue, 15 Feb 2011 00:30:40 +0100 4474350 http://www.medworm.com/index.php?rid=4474349&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21285529%26dopt%3DAbstract Authors: Borsos E, Erdélyi P, Vellai T Apoptosis, the main form of regulated (or programmed) cell death, allows the organism to tightly control cell numbers and tissue size, and to protect itself from potentially damaging cells. This type of cellular self-killing has long been assumed to be essential for early development. In the nematode Caenorhabditis elegans, however, the core apoptotic cell death pathway appears to be dispensable for embryogenesis when most developmental cell deaths take place: mutant nematodes defective for apoptosis develop into adulthood, with superficially normal morphology and behavior. Accumulating evidence indicates a similar situation in mammalian systems as well. For example, apoptosis-deficient mice can grow as healthy, fertile adults. These observations... Autophagy journals http://www.medworm.com/rss/comments.php?id=4474349 Tue, 15 Feb 2011 00:30:34 +0100 4474349 http://www.medworm.com/index.php?rid=4474348&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21293178%26dopt%3DAbstract Authors: Jegga AG, Schneider L, Ouyang X, Zhang J The mechanisms of the control and activity of the autophagy-lysosomal protein degradation machinery is emerging as an important theme for neurodevelopment and neurodegeneration. However, the underlying regulatory and functional networks of known genes controlling autophagy and lysosomal function and their role in disease are relatively unexplored. We performed a systems biology-based integrative computational analysis to study the interactions between molecular components and to develop models for regulation and function of genes involved in autophagy and lysosomal function. Specifically, we analyzed transcriptional and microRNA-based posttranscriptional regulation of these genes and performed functional enrichment analyses to understan... Autophagy journals http://www.medworm.com/rss/comments.php?id=4474348 Tue, 15 Feb 2011 00:30:18 +0100 4474348 http://www.medworm.com/index.php?rid=4474347&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21301205%26dopt%3DAbstract Authors: Luciani MF, Giusti C, Harms B, Oshima Y, Kikuchi H, Kubohara Y, Golstein P We investigated the role of atg1 in autophagic cell death (ACD) in a Dictyostelium monolayer model. The model is especially propitious, not only because of genetic tractability and absence of apoptosis machinery, but also because induction of ACD requires two successive exogenous signals, first the combination of starvation and cAMP, second the differentiation factor DIF-1. This enables one to analyze separately first-signal-induced autophagy and subsequent second-signal-induced ACD. We used mutants of atg1, a gene that plays an essential role in the initiation of autophagy. Upon starvation/cAMP, in contrast to parental cells, atg1 mutant cells showed irreversible lesions, clearly establishing a protect... Autophagy journals http://www.medworm.com/rss/comments.php?id=4474347 Tue, 15 Feb 2011 00:30:09 +0100 4474347 http://www.medworm.com/index.php?rid=4411755&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21242722%26dopt%3DAbstract Authors: Ke PY, Chen SS Autophagy is an evolutionarily conserved process that catabolizes intracellular components and maintains cellular homeostasis. Autophagy involves the sequestration of cytoplasmic content within a double-membraned autophagosome, and the fusion of the autophagosome with a lysosome to form an autolysosome for subsequent degradation (Fig. 1A). Autophagy plays a pivotal role in various aspects of cellular responses to stresses, such as nutrient deprivation, damaged organelles, aggregated proteins, exposure to endoplasmic reticulum (ER) stress, and pathogen infections. Virus infection often leads to ER stress and induction of the unfolded protein response (UPR). Recent studies reveal that virus-induced UPR may activate autophagy to support the virus life cycle. Howeve... Autophagy journals http://www.medworm.com/rss/comments.php?id=4411755 Sat, 29 Jan 2011 02:15:10 +0100 4411755 http://www.medworm.com/index.php?rid=4411754&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21266843%26dopt%3DAbstract Authors: Fan QW, Weiss WA Signaling through phosphatidylinositol 3-kinase (PtdIns3K)-Akt-mTOR is frequently activated in cancers including glioblastoma multiforme (GBM), where this kinase network regulates survival. It is thus surprising that inhibitors of these pathways induce minimal cell death in glioma. We showed that the dual PtdIns3K-mTOR inhibitor PI-103 induces autophagy in therapy-resistant, PTEN-mutant glioma, with blockade of mTOR complex 1 (mTORC1) and complex 2 (mTORC2) contributing independently to autophagy. Inhibition of autophagosome maturation synergizes with PI-103 to induce apoptosis through the Bax-dependent intrinsic mitochondrial pathway, indicating that PI-103 induces autophagy as a survival pathway in this setting. Not all inhibitors of PtdIns3K-Akt-mTOR signal... Autophagy journals http://www.medworm.com/rss/comments.php?id=4411754 Sat, 29 Jan 2011 02:15:07 +0100 4411754 http://www.medworm.com/index.php?rid=4343825&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21150268%26dopt%3DAbstract Authors: Shen HM, Codogno P The concept of autophagic cell death was first established based on observations of increased autophagic markers in dying cells. The major limitation of such a morphology-based definition of autophagic cell death is that it fails to establish the functional role of autophagy in the cell death process, and thus contributes to the confusion in the literature regarding the role of autophagy in cell death and cell survival. Here we propose to define autophagic cell death as a modality of non-apoptotic or necrotic programmed cell death in which autophagy per se serves as a cell death mechanism, upon meeting the following set of criteria: (i) cell death occurs without the involvement of apoptosis; (ii) there is an increase of autophagic flux, and not just an incre... Autophagy journals http://www.medworm.com/rss/comments.php?id=4343825 Fri, 14 Jan 2011 13:30:08 +0100 4343825 http://www.medworm.com/index.php?rid=4088889&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20962583%26dopt%3DAbstract Authors: Michael D, Ginger ML, Brennand A, Gualdrón-López M, Colombo MI, Coombs GH, Coppens I, Jayabalasingham B, Langsley G, de Castro SL, Menna-Barreto R, Mottram JC, Navarro M, Rigden DJ, Romano PS, Stoka V, Turk B, Michels PA Autophagy is the degradative process by which eukaryotic cells digest their own components using acid hydrolases within the lysosome. Originally thought to function almost exclusively in providing starving cells with nutrients taken from their own cellular constituents, autophagy is in fact involved in numerous cellular events including differentiation, turnover of macromolecules and organelles and defense against parasitic invaders. During the past 10-20 years, molecular components of the autophagic machinery have been discovered, revealing a complex intera... Autophagy journals http://www.medworm.com/rss/comments.php?id=4088889 Sat, 23 Oct 2010 21:45:06 +0100 4088889 http://www.medworm.com/index.php?rid=4065652&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20935487%26dopt%3DAbstract Authors: Ktistakis NT, Andrews S, Long J We have recently proposed that some autophagosomes are formed within omegasomes, membrane sites connected to the endoplasmic reticulum and enriched in phosphatidylinositol 3-phosphate. In order to understand if there is any biological advantage to having such a precursor in autophagosome biogenesis, we generated a simple computer program that simulates omegasome and autophagosome formation under a variety of conditions. We concluded from running this simulation that having a transient precursor permits a bigger dynamic range of the autophagic response and allows a more efficient approach to steady state after autophagy stimulation. PMID: 20935487 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4065652 Thu, 14 Oct 2010 12:10:15 +0100 4065652 http://www.medworm.com/index.php?rid=4065651&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20935505%26dopt%3DAbstract Authors: Chen ZF, Li YB, Han JY, Wang J, Yin JJ, Li JB, Tian H Autophagy is an intracellular catabolic system, which enables cells to capture cytoplasmic components for degradation within lysosomes. Autophagy is involved in development, differentiation and tissue remodeling in various organisms, and is also implicated in certain diseases. Recent studies demonstrate that autophagy is necessary to maintain architecture and function of pancreatic beta cells. Altered autophagy is also involved in pancreatic beta cell death. Whether autophagy plays a protective or harmful role in diabetes is still not clear. In this review, we will summarize the current knowledge about the role of autophagy in pancreatic beta cell and diabetes. PMID: 20935505 [PubMed - as supplied by publisher] (Source:... Autophagy journals http://www.medworm.com/rss/comments.php?id=4065651 Thu, 14 Oct 2010 12:10:11 +0100 4065651 http://www.medworm.com/index.php?rid=4065650&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20935516%26dopt%3DAbstract Authors: Gonzalez CD, Lee MS, Marchetti P, Pietropaolo M, Towns R, Vaccaro MI, Watada H, Wiley JW An emerging body of evidence supports a role for autophagy in the pathophysiology of type 1 and type 2 diabetes mellitus. Persistent high concentrations of glucose lead to imbalances in the antioxidant capacity within the cell resulting in oxidative stress-mediated injury in both disorders. An anticipated consequence of impaired autophagy is the accumulation of dysfunctional organelles such as mitochondria within the cell. Mitochondria are the primary site of the production of reactive oxygen species (ROS), and an imbalance in ROS production relative to the cytoprotective action of autophagy may lead to the accumulation of ROS. Impaired mitochondrial function associated with increased ROS ... Autophagy journals http://www.medworm.com/rss/comments.php?id=4065650 Thu, 14 Oct 2010 12:10:07 +0100 4065650 http://www.medworm.com/index.php?rid=4045652&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20890115%26dopt%3DAbstract Role of selective autophagy in cellular remodeling: "Self-eating" into shape. Autophagy. 2010 Nov 31;6(8) Authors: Kadandale P, Kiger AA The Atg1 Ser/Thr kinase, although now a well-established regulator of autophagy, was first identified genetically in C. elegans as a requirement for axonal elongation. However, possible connections between Atg1 functions in cellular morphogenesis and in autophagy were previously unaddressed. In the recent paper highlighted in this punctum, we reconciled these dual roles for Atg1, demonstrating a requirement for p62-mediated selective autophagy in the dynamic regulation of cell shape, in both fly and mammalian macrophages, with effects on immune cell functions. This work further strengthens the emerging importance of autophagy as a post-transla... Autophagy journals http://www.medworm.com/rss/comments.php?id=4045652 Sat, 09 Oct 2010 06:50:07 +0100 4045652 http://www.medworm.com/index.php?rid=4000130&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20861670%26dopt%3DAbstract Authors: Kwon SI, Cho HJ, Park OK The vascular system of plants consists of two conducting tissues, xylem and phloem, which differentiate from procambium cells. Xylem serves as a transporting system for water and signaling molecules and is formed by sequential developmental processes, including cell division/expansion, secondary cell wall deposition, vacuole collapse and programmed cell death (PCD). PCD during xylem differentiation is accomplished by degradation of cytoplasmic constituents, and it is required for the formation of hollow vessels, known as tracheary elements (TEs). Our recent study revealed that the small GTPase RabG3b acts as a regulator of TE differentiation through its autophagic activation. By using an Arabidopsis in vitro cell culture system, we showed that autophag... Autophagy journals http://www.medworm.com/rss/comments.php?id=4000130 Sat, 25 Sep 2010 12:06:29 +0100 4000130 http://www.medworm.com/index.php?rid=4000129&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20861674%26dopt%3DAbstract Authors: Ravikumar B, Moreau K, Rubinsztein DC The membrane origin of autophagosomes has long been a mystery and it may involve multiple sources. In this punctum, we discuss our recent finding that the plasma membrane contributes to the formation of pre-autophagic structures via clathrin-mediated endocytosis. Our study suggests that Atg16L1 interacts with clathrin heavy-chain/AP2 and is also localized on vesicles (positive for clathrin or cholera toxin B) close to the plasma membrane. Live-cell imaging studies revealed that the plasma membrane contributes to Atg16L1-positive structures and that this process and autophagosome formation are impaired by knockdowns of genes regulating clathrin-mediated endocytosis. PMID: 20861674 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=4000129 Sat, 25 Sep 2010 12:06:25 +0100 4000129 http://www.medworm.com/index.php?rid=4000128&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20864809%26dopt%3DAbstract Authors: Houslay MD, Christian F Cells employ macroautophagy to deliver aggregates of misfolded and/or ubiquitinated proteins for lysosomal degradation or supply of essential macromolecules under conditions of nutrient deprivation. The former seems complementary to the proteasome system, which is likely to degrade only soluble proteins. While bulk degradation via the autophagy pathway during starvation is rather nonspecific, the recognition of proteins that are either misfolded or adopt a particular conformation and/or become ubiquitinated, requires some form of specificity. This is brought about, at least in part, by the scaffold and ubiquitinbinding protein, p62 (SQSTM1). p62 is a multidomain scaffold that sequesters other proteins and polymerizes through its Phox and Bem1p domains a... Autophagy journals http://www.medworm.com/rss/comments.php?id=4000128 Sat, 25 Sep 2010 12:06:21 +0100 4000128 http://www.medworm.com/index.php?rid=4000127&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20864812%26dopt%3DAbstract Authors: McPhee CK, Baehrecke EH Autophagy is a process to degrade and recycle cytoplasmic contents. Autophagy is required for survival in response to starvation, but has also been associated with cell death. How autophagy functions during cell survival in some contexts and cell death in others is unknown. Drosophila larval salivary glands undergo programmed cell death requiring autophagy genes, and are cleared in the absence of known phagocytosis. Recently, we demonstrated that Draper (Drpr), the Drosophila homolog of C. elegans engulfment receptor CED-1, is required for autophagy induction during cell death, but not during cell survival. drpr mutants fail to clear salivary glands. drpr knockdown in salivary glands prevents the induction of autophagy, and Atg1 misexpression in drpr nu... Autophagy journals http://www.medworm.com/rss/comments.php?id=4000127 Sat, 25 Sep 2010 12:06:13 +0100 4000127 http://www.medworm.com/index.php?rid=4000126&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20864818%26dopt%3DAbstract Authors: Zhou L, Liu F Accumulating evidence strongly suggests that autophagy, which is induced by endoplasmic reticulum (ER) stress in adipocytes, may play an important role in obesity-induced insulin resistance and type 2 diabetes. Obesity induces ER stress in mouse adipose tissue, which correlates with reduced adiponectin levels. In 3T3-L1 adipocytes, induction of ER stress is sufficient to promote autophagy-dependent adiponectin degradation. In contrast, suppressing ER stress increases adiponectin levels in 3T3-L1 adipocytes and alleviates high fat diet-induced adiponectin downregulation in mice. The ER stress-induced adiponectin downregulation can also be suppressed by overexpression of DsbA-L, a newly identified protein involved in promoting adiponectin multimerization and stabil... Autophagy journals http://www.medworm.com/rss/comments.php?id=4000126 Sat, 25 Sep 2010 12:06:08 +0100 4000126 http://www.medworm.com/index.php?rid=3734420&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20603599%26dopt%3DAbstract Authors: Zimmermann AC, Zarei M, Eiselein S, Dengjel J Stress-induced autophagy leads to major cellular remodeling. During autophagy, a new organelle, the autophagosome, is formed that shuttles cellular material to lysosomes for degradation. Quantitative mass spectrometry-based proteomics is a powerful research strategy for the description of spatio-temporal protein dynamics during autophagy. This technique allows the identification of protein-protein interactions and of specific post-translational modifications. In addition, current methods enable the in-depth characterization of cellular as well as organellar composition changes and the global analysis of signaling networks. Thus, a plastic picture of the cell can be drawn. In this review we describe recent advances in MS-based prote... Autophagy journals http://www.medworm.com/rss/comments.php?id=3734420 Fri, 09 Jul 2010 03:48:08 +0100 3734420 http://www.medworm.com/index.php?rid=3610621&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20505317%26dopt%3DAbstract Authors: Dewaele M, Maes H, Agostinis P Mounting evidence suggests that reactive oxygen species (ROS) are multifaceted signaling molecules implicated in a variety of cellular programs during physiological as well as pathological conditions. Recently, ROS produced endogenously, by deranged metabolism of cancer cells, or exogenously, by ROS-generating drugs, have been shown to promote macroautophagy, a lysosomal pathway of selfdegradation with essential prosurvival functions. Several molecular aspects of the modulation of autophagy pathways by ROS have been revealed in the past years and it is now clear that these processes are mutually linked and play a crucial role in cancer progression and in response to cancer therapeutics. In this review we address the molecular mechanisms underlyin... Autophagy journals http://www.medworm.com/rss/comments.php?id=3610621 Sat, 29 May 2010 22:03:09 +0100 3610621 http://www.medworm.com/index.php?rid=3582441&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20484985%26dopt%3DAbstract Authors: Ziviani E, Whitworth AJ Much evidence links mitochondrial dysfunction to the death of neurons in Parkinson disease (PD), and is particularly emphasized by our growing understanding of the function of genes linked to recessively inherited PD such as PINK1, parkin and DJ-1. Recent work has revealed an exciting link between the PINK1-Parkin pathway and the autophagic turnover of dysfunctional mitochondrial (mitophagy). We have recently shown that mitofusin is ubiquitinated by Parkin when it is recruited to dysfunctional mitochondria. Recent work also shows that regulated fission and fusion events help segregate dysfunctional mitochondria prior to mitophagy. Here we hypothesize how Parkin-mediated ubiquitination of Mfn may play a role in this mechanism. PMID: 20484985 [PubMed ... Autophagy journals http://www.medworm.com/rss/comments.php?id=3582441 Fri, 21 May 2010 11:54:06 +0100 3582441 http://www.medworm.com/index.php?rid=3556945&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20458170%26dopt%3DAbstract We present a straightforward assay for autophagy which combines the sensitivity of the EGFP-LC3 reporter protein with the throughput capacity and quantitative power of flow cytometry. Because saponin extraction is specific for the non-autophagosome-associated EGFP-LC3-I form of the protein, flow cytometry can be used to measure total fluorescence of saponin-extracted HOS-EGFP-LC3 cells as a measure of the levels of autophagosome-associated EGFP-LC3-II. Combined with inhibitors of degradation, we have adapted this assay to differentiate between constitutive and induced autophagy and to quantify the changes in flux of the system. Moreover, using direct antibody staining for the endogenous LC3 protein, we have extended this assay to the detection of autophagosome formation in nontransfected c... Autophagy journals http://www.medworm.com/rss/comments.php?id=3556945 Thu, 13 May 2010 01:38:20 +0100 3556945 http://www.medworm.com/index.php?rid=3556944&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20458173%26dopt%3DAbstract Authors: Koch JC, Knöferle J, Tönges L, Ostendorf T, Bähr M, Lingor P Axonal degeneration is a pathological hallmark of many traumatic and neurodegenerative neurological disorders. Although the underlying mechanisms remain largely unclear, increased autophagy and the influx of extracellular calcium have been implicated in the pathogenesis of axonal degeneration based on in vitro data. Using in vivo imaging of the rat optic nerve after crush lesion we could now show that both mechanisms are linked and play an important role in acute axonal degeneration in vivo. Our data suggest that crush lesion of the optic nerve induces a rapid calcium influx through calcium channels, which results in a secondary induction of autophagy that participates actively in axonal degradation. Therape... Autophagy journals http://www.medworm.com/rss/comments.php?id=3556944 Thu, 13 May 2010 01:38:17 +0100 3556944 http://www.medworm.com/index.php?rid=3556943&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20458181%26dopt%3DAbstract Authors: Puissant A, Auberger P Resveratrol (RSV) is an attractive candidate for cancer therapy because of its ability to intervene at different levels in the AMPK/mTOR pathway. Indeed, RSV is unique in its capacity to inhibit both mTOR and S6 kinase and to activate AMPK. Our recent data reveals that RSV triggered autophagic cell death (ACD) in Chronic Myelogenous Leukemia (CML) cells, via both AMPK activation and JNK-mediated p62/SQSTM1 expression. Here we discuss how Resveratrol can mediate ACD in CML cells and the possibility of utilizing the AMPK/mTOR and JNK/p62 pathways via Resveratrol to combat CML and other hematopoietic malignancies. PMID: 20458181 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=3556943 Thu, 13 May 2010 01:38:14 +0100 3556943 http://www.medworm.com/index.php?rid=3556942&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20458183%26dopt%3DAbstract Authors: Sun Y, Grabowski GA PMID: 20458183 [PubMed - as supplied by publisher] (Source: Autophagy) Autophagy journals http://www.medworm.com/rss/comments.php?id=3556942 Thu, 13 May 2010 01:38:11 +0100 3556942 http://www.medworm.com/index.php?rid=3556941&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20458184%26dopt%3DAbstract Authors: Suzuki HI, Kiyono K, Miyazono K Transforming growth factor-beta (TGFbeta) has broad impacts on an array of diverse cellular functions including cell growth, differentiation, adhesion, migration and apoptosis. Perturbations of the TGFbeta signaling pathways are involved in progression of various tumors. Autophagy is a pivotal response of normal and cancer cells to environmental stresses and is induced by various stimuli. Otherwise, autophagy has an intrinsic function in tumor suppression. Recently, we demonstrated that TGFbeta induces autophagy in hepatocellular carcinoma cells and mammary carcinoma cells. Autophagy activation by TGFbeta is mediated through the Smad and JNK pathways. We show that siRNA-mediated knockdown of autophagy genes suppresses the growth inhibitory funct... Autophagy journals http://www.medworm.com/rss/comments.php?id=3556941 Thu, 13 May 2010 01:38:07 +0100 3556941 http://www.medworm.com/index.php?rid=3522931&cid=s_37572_171_f&fid=37572&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20431342%26dopt%3DAbstract Authors: Chen SY, Maa MC, Chiu LY, Wang JS, Chien CL, Lin WW A previous report showed that the pan-caspase inhibitor zVAD can induce necrosis accompanied by autophagosome formation in L929 fibrosarcoma cells. Such autophagic cell death relies on caspase 8 inhibition and ROS accumulation. Since the connection of these molecules is still poorly understood, we explored the underlying signaling cascades in this event. First, we confirmed zVAD can stimulate LC3 cleavage, beclin 1 gene expression, autophagosome formation, and ROS accumulation in L929 cells. Antioxidants, Beclin 1 or Atg5 silencing, and class III PtdIns3K inhibitors all effectively blocked ROS production and cell death, suggesting ROS accumulation downstream of autophagy contributes to cell necrosis. zVAD also stimulated PARP... Autophagy journals http://www.medworm.com/rss/comments.php?id=3522931 Sat, 01 May 2010 20:02:15 +0100 3522931