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Self-killing of melanoma cells by cytosolic delivery of dsRNA: Wiring innate immunity for a coordinated mobilization of endosomes, autophagosomes and the apoptotic machinery in tumor cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Patients with metastatic melanoma have a poor prognosis, primarily due to a generalized inefficacy of current anticancer treatments. Therefore, the identification of novel death inducers with good bioavailability and safety profiles is a main priority in this disease. Here we summarize recent work from our group uncovering an unexpected ability of the dsRNA mimic polyinosine-polycytidylic acid (pIC) to engage the endo/lysosomal machinery of melanoma cells and induce their self degradation by autophagy and apoptosis, without noticeable secondary effects in vivo. However the antimelanoma activity of pIC strictly required...
Source: Autophagy - November 20, 2009 Category: Cytology Authors: Alonso-Curbelo D, Soengas MS Tags: Autophagy Source Type: journals

The cysteine protease MoAtg4 interacts with MoAtg8 and is required for differentiation and pathogenesis in Magnaporthe oryzae.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Atg4 is a unique cysteine protease responsible for the cleavage of the carboxyl terminus of Atg8 during the formation of autophagosomes in yeast. Here we report that MoAtg4, an Atg4 homologue in Magnaporthe oryzae, controls cell differentiation and pathogenicity by interacting with MoAtg8, an autophagic protein essential for autophagic cell death and pathogenicity. Yeast complementation assay revealed that MoATG4 can functionally complement the defects of the yeast ATG4 deletion mutant. The direct interaction between MoAtg4 and MoAtg8 was detected in both yeast two hybrid and bimolecular fluorescence complementation (B...
Source: Autophagy - November 20, 2009 Category: Cytology Authors: Liu TB, Liu XH, Lu JP, Zhang L, Min H, Lin FC Tags: Autophagy Source Type: journals

Investigating autophagy: Quantitative morphometric analysis using electron microscopy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is a compensatory pathway involving isolation and subsequent degradation of cytosolic material and organelles in eukaryotic cells.(1) The autophagic process can provide a "housekeeping" function by removing damaged proteins and organelles in a selective or nonselective fashion in order to exert a protective effect following stress.(2) Remarkably, after being discovered to be much more of a targeted process than a random one, the role of autophagy became implicated in many normal cellular and disease processes.(3) Several methodologies are routinely employed to monitor the entire autophagic process.(4) Microtu...
Source: Autophagy - November 20, 2009 Category: Cytology Authors: Swanlund JM, Kregel KC, Oberley TD Tags: Autophagy Source Type: journals

Autophagy augmented by troglitazone is independent of EGFR transactivation and correlated with AMP-activated protein kinase signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report here that troglitazone augments AMP-activated protein kinase-alpha (AMPKalpha) phosphorylation, reduces p70S6 kinase phosphorylation and stimulates autophagy that is independent of EGFR expression and transactivation. Troglitazone stimulus reduced neither lysosomal staining nor GFP-LC3 dots of HeLa cells, when the cells pretreated with AG1478, a specific EGFR kinase inhibitor. Furthermore, AG1478 additively enhanced the troglitazone-induced degradation of sequestosome 1 (SQSTM1/p62), which is a selective substrate of autophagy. Inhibition of AMPKalpha activity either by compound C or by RNA interference markedly ...
Source: Autophagy - November 20, 2009 Category: Cytology Authors: Yan J, Yang H, Wang G, Sun L, Zhou Y, Guo Y, Xi Z, Jiang X Tags: Autophagy Source Type: journals

Control of basal autophagy by calpain1 mediated cleavage of ATG5.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy functions as an important catabolic mechanism by mediating the turnover of intracellular organelles and protein complexes. Although the induction of autophagy by starvation has been extensively studied, we still understand very little about how autophagy is regulated under normal nutritional conditions. Here we describe a study using a small molecule autophagy inducer, fluspirilene, as a tool to explore the mechanism of autophagy induction in normal living cells. We confirm the activity of fluspirilene in inhibiting Ca(2+) flux. Furthermore, we show that reducing intracellular Ca(2+) prevents the cleavage of ...
Source: Autophagy - November 13, 2009 Category: Cytology Authors: Xia HG, Zhang L, Chen G, Zhang T, Liu J, Jin M, Ma X, Ma D, Yuan J Tags: Autophagy Source Type: journals

Artificial induction of autophagy around polystyrene beads in nonphagocytic cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is an intracellular event that acts as an innate cellular defense mechanism to kill invading bacteria such as group A Streptococcus in nonphagocytic epithelial-like cells. The cellular events underlying autophagosome formation upon bacterial invasion remain unclear due to the biochemical complexity associated with uncharacterized bacterial components, and the difficulty of predicting the location as well as the timing of where/when autophagosome formation will take place. To overcome these problems, we monitored autophagosome formation in living nonphagocytic cells by inducing autophagy around artificial micr...
Source: Autophagy - November 13, 2009 Category: Cytology Authors: Kobayashi S, Kojidani T, Osakada H, Yamamoto A, Yoshimori T, Hiraoka Y, Haraguchi T Tags: Autophagy Source Type: journals

Bacillus calmette-guerin cell wall cytoskeleton enhances colon cancer radiosensitivity through autophagy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guerin (BCG/CWS) is an effective antitumor immunotherapy agent. Here, we demonstrate that BCG/CWS has a radiosensitizing effect on colon cancer cells through the induction of autophagic cell death. Exposure of HCT116 colon cancer cells to BCG/CWS before ionizing radiation (IR) resulted in increased cell death in a caspase-independent manner. Treatment with BCG/CWS plus IR resulted in the induction of autophagy in colon cancer cells. Either the autophagy inhibitor 3-methyladenine or knockdown of beclin 1 or Atg7 significantly reduced tumor cell death induce...
Source: Autophagy - November 13, 2009 Category: Cytology Authors: Yuk JM, Shin DM, Song KS, Lim K, Kim KH, Lee SH, Kim JM, Lee JS, Paik TH, Kim JS, Jo EK Tags: Autophagy Source Type: journals

Methods to monitor autophagy in H. pylori vacuolating cytotoxin A (VacA)-treated cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Helicobacter pylori is a gram negative pathogen that infects at least half of the world's population and is associated not only with gastric cancer but also with other diseases such as gastritis and peptic ulcers. Indeed, H. pylori is considered the single most important risk factor for the development of gastric cancer. The vacuolating cytotoxin VacA, secreted by H. pylori, promotes intracellular survival of the bacterium and modulates host immune responses. In a recent study, we reported that VacA induces autophagy. Multilamellar autophagosomes are detected in gastric epithelial cells that are distinct from the large...
Source: Autophagy - November 3, 2009 Category: Cytology Authors: Raju D, Jones NL Tags: Autophagy Source Type: journals

Listeria monocytogenes ActA is a key player in evading autophagic recognition.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is a pivotal bulk degradation system that eliminates undesirable molecules, damaged organelles, and misfolded protein aggregates in response to diverse stimuli, including infection. Autophagy acts to limit intracellular microbial growth but intracellular pathogens have evolved strategies to subvert host autophagic responses for their survival. We found that Listeria monocytogenes ActA, a surface protein required for actin polymerization and actin-based bacterial motility, plays a pivotal role in evading autophagy, but in a manner independent of bacterial motility. We show that L. monocytogenes exploits the bi...
Source: Autophagy - October 27, 2009 Category: Cytology Authors: Yoshikawa Y, Ogawa M, Hain T, Chakraborty T, Sasakawa C Tags: Autophagy Source Type: journals

Assessing autophagy in the context of photodynamic therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This report explores the following issues: (1) Does the induction of autophagy in PDT protocols occur independent of, or in association with, apoptosis? (2) Does the resulting autophagy play a prosurvival or prodeath role? (3) Do photosensitizers damage/inactivate specific proteins that are components of, or that modulate the autophagic process? (4) Can an autophagic response be mounted in cells in which lysosomes are specifically photodamaged? In brief, autophagy can occur independently of apoptosis in PDT protocols, and appears to play a prosurvival role in apoptosis competent cells, and a prodeath role in apoptosis inco...
Source: Autophagy - October 27, 2009 Category: Cytology Authors: Reiners JJ, Agostinis P, Berg K, Oleinick NL, Kessel D Tags: Autophagy Source Type: journals

Autophagy eliminates a specific species of misfolded procollagen and plays a protective role in cell survival against ER stress.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Type I collagen is one of the most abundant proteins in the human body and is essential for tissue formation. Mutations in collagen cause severe abnormalities in bone formation, including osteogenesis imperfecta. Although the mutant collagens are retained in the endoplasmic reticulum (ER) and are toxic to the cell, little is known about how they are removed from the ER. Using two independent cell lines that produce misfolded collagens, we recently demonstrated that procollagen, which is misfolded and accumulated as trimers, is eliminated through the autophagy-lysosomal pathway, not through the ER-associated degradation...
Source: Autophagy - October 16, 2009 Category: Cytology Authors: Ishida Y, Nagata K Tags: Autophagy Source Type: journals

Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is a highly conserved catabolic process for the elimination and recycling of organelles and macromolecules, characterized by the formation of double-membrane vesicles called autophagosomes. To date, the function of autophagy in cell differentiation is poorly documented. Here, we investigated the possibility that megakaryocytic differentiation of the Chronic Myelogenous Leukemia (CML) cell line K562, a process known to be accompanied by accumulation of vacuoles inside the cells, might involve autophagy. Using various complementary approaches, we show that the combination of the phorbol ester PMA and the p38(MA...
Source: Autophagy - October 1, 2009 Category: Cytology Authors: Colosetti P, Puissant A, Robert G, Luciano F, Jacquel A, Gounon P, Cassuto JP, Auberger P Tags: Autophagy Source Type: journals

Parkinson disease, LRRK2 and the endocytic-autophagic pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19770575 [PubMed - as supplied by publisher] (Source: Autophagy)
Source: Autophagy - September 24, 2009 Category: Cytology Authors: Alegre-Abarrategui J, Wade-Martins R Tags: Autophagy Source Type: journals

Autophagy, senescence and tumor dormancy in cancer therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The relationships between autophagy and apoptosis have been examined quite extensively and have often been shown to be reciprocally regulated responses to stresses such as exposure of tumor cells to chemotherapeutic drugs and radiation. However, there is now evidence that autophagy may also play a role in tumor dormancy. Given that tumor dormancy and disease recurrence are poorly understood phenomena which are nevertheless critical elements of patient morbidity and mortality, this commentary develops the postulate that autophagy and senescence may be coupled responses that influence the capacity of the tumor cell to ma...
Source: Autophagy - September 24, 2009 Category: Cytology Authors: Gewirtz DA Tags: Autophagy Source Type: journals

Self-consuming innate immunity in Arabidopsis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Programmed cell death (PCD) associated with the pathogen-induced hypersensitive response (HR) is a hallmark of plant innate immunity. HR PCD is triggered upon recognition of pathogen effector molecules by host immune receptors either directly or indirectly via effector modulation of host targets. However, it has been unclear by which molecular mechanisms plants execute PCD during innate immune responses. We recently examined HR PCD in autophagy-deficient Arabidopsis knockout mutants (atg) and find that PCD conditioned by one class of plant innate immune receptors is suppressed in atg mutants. Intriguingly, HR triggered...
Source: Autophagy - September 24, 2009 Category: Cytology Authors: Hofius D, Mundy J, Petersen M Tags: Autophagy Source Type: journals

Trypanosoma brucei ATG8: Structural insights into autophagic-like mechanisms in protozoa.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Bioinformatic searches of genome databases revealed that the number of autophagy-related genes (ATG) is considerably lower in trypanosomes than in higher eukaryotes and even in yeast. This raises the question of whether autophagy in this protozoan parasite is more primitive and represents a rudimentary paradigm due to its early branching off the evolutionary tree. We here present the crystal structure of TbATG8B. This molecule (MW 13.7 kDa) belongs to the ubiquitin-like proteins showing the typical ubiquitin fold and strong sequence homology to LC3, the human homologue. Due to its characteristic folding, it should read...
Source: Autophagy - September 9, 2009 Category: Cytology Authors: Koopmann R, Muhammad K, Perbandt M, Betzel C, Duszenko M Tags: Autophagy Source Type: journals

Chaperone-mediated autophagy: The heretofore untold story of J. Fred "Paulo" Dice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19617700 [PubMed - as supplied by publisher] (Source: Autophagy)
Source: Autophagy - July 21, 2009 Category: Cytology Authors: Klionsky DJ, Dice JF Tags: Autophagy Source Type: journals

Inhibition of p38alpha unveils an AMPK-FoxO3A axis linking autophagy to cancer-specific metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is an essential process for the maintenance of cellular and metabolic homeostasis. Indeed, it is required for the recovery of ATP-generating substrates in cells subjected to different types of stress insults. Thus, the activity of the autophagic machinery strongly depends on the metabolic status of the cell.(1) It has been proposed that this principle applies not only to normal, but also to cancer cells,(2) despite the profound differences in their metabolism. Cancer cells predominantly produce ATP through the constitutive activation of aerobic glycolysis, a process that generally relies on the stabilization ...
Source: Autophagy - July 10, 2009 Category: Cytology Authors: Chiacchiera F, Simone C Tags: Autophagy Source Type: journals

Autophagy is not universally required for phosphatidyl-serine exposure and apoptotic cell engulfment during neural development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined retinas at embryonic day 5, an early stage at which cell death is related to eye morphogenesis and to retinal ganglion cell generation, as well as at embryonic day 9, when cell death is associated with neurotrophic support of the retinal ganglion cells. Exposure to 3-methyl-adenine, a classical inhibitor of autophagy, elicited a selective accumulation of apoptotic bodies in the dorsotemporal area of embryonic day 5 retinas where neurogenesis is taking place. This accumulation was correlated with a blockage of phosphatidyl-serine presentation and, consequently, with a lack of engulfment of the dying cells by the...
Source: Autophagy - July 10, 2009 Category: Cytology Authors: Mellén MA, de la Rosa EJ, Boya P Tags: Autophagy Source Type: journals

Autophagy maintains cardiac function in the starved adult.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
To examine the functional significance and detailed morphological characteristics of starvation-induced autophagy in the adult heart, we starved green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) transgenic mice for up to 3 days. Electron microscopy revealed that, after as little as 12 hours of starvation, round and homogenously electron-dense lipid droplet-like vacuoles appeared in cardiomyocytes. These were determined to be lysosomes based on cathepsin D immunopositivity and acid phosphatase activity. The number of these lysosomes increased with starvation time, and typical autolysos...
Source: Autophagy - July 10, 2009 Category: Cytology Authors: Takemura G, Kanamori H, Goto K, Maruyama R, Tsujimoto A, Fujiwara H, Seishima M, Minatoguchi S Tags: Autophagy Source Type: journals

Autophagy is required for tolerance of drought and salt stress in plants.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is a protein degradation process in which cells recycle cytoplasmic contents when subjected to environmental stress conditions or during certain stages of development. Upon the induction of autophagy, a double membrane autophagosome forms around cytoplasmic components and delivers them to the vacuole or lysosome for degradation. In plants, autophagy has been shown previously to be induced during abiotic stresses including nutrient starvation and oxidative stress. In this paper, we demonstrate the induction of autophagy in high salt and osmotic stress conditions, concomitant with the upregulation of expression...
Source: Autophagy - July 10, 2009 Category: Cytology Authors: Liu Y, Xiong Y, Bassham DC Tags: Autophagy Source Type: journals

A combined proteomic and genetic analysis identifies a role for the lipid desaturase Desat1 in starvation-induced autophagy in Drosophila.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is a lysosomal-mediated degradation process that promotes cell survival during nutrient-limiting conditions. However, excessive autophagy results in cell death. In Drosophila, autophagy is regulated nutritionally, hormonally and developmentally in several tissues, including the fat body, a nutrient-storage organ. Here we use a proteomics approach to identify components of starvation-induced autophagic responses in the Drosophila fat body. Using cICAT() labeling and mass spectrometry, differences in protein expression levels of normal compared to starved fat bodies were determined. Candidates were analyzed gen...
Source: Autophagy - July 10, 2009 Category: Cytology Authors: Köhler K, Brunner E, Guan XL, Boucke K, Greber UF, Mohanty S, Barth JM, Wenk MR, Hafen E Tags: Autophagy Source Type: journals

Morphological homeostasis by autophagy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
With cellular organelles coming in all shapes and sizes, the principle 'form follows function' is readily discernible through the cytologist's lens. Architecturally, one might ask whether there is feedback in this organization. Does a cell 'know' when it has constructed membrane into the stacks of the Golgi, the cisternae of the mitochondria or the tubules of the endoplasmic reticulum? Proofreading can occur in vivo as both errors in nucleic acids and misfolds in proteins are recognized by the cell. Are there analogous systems which maintain/regulate the architectural integrity of organelles? Our recent paper entitled ...
Source: Autophagy - July 10, 2009 Category: Cytology Authors: Lingwood D, Schuck S, Ferguson C, Gerl M, Simons K Tags: Autophagy Source Type: journals

Autophagy in food biotechnology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The purpose of this review is not to explain autophagy (as clearly there is a plethora of reviews and research papers on the topic) but to provide the autophagy-savvy reader with an overview of the impact of autophagy research on a number of current topics in food biotechnology. To understand this connection, we need to remember that autophagy is, at the end of the day, a type of stress response. Since as humans we are heterotrophic eukaryotic organisms, our cells, and the cells of those organisms that we consume, use autophagy as part of the day-to-day business of living. Thus, a number of food biotechnology processes...
Source: Autophagy - June 29, 2009 Category: Cytology Authors: Abeliovich H, Gonzalez R Tags: Autophagy Source Type: journals

MgAtg9 trafficking in Magnaporthe oryzae.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is a vacuolar/lysosomal cytoplasmic recycling system in eukaryotic cells. ScATG9 is indispensable for autophagy in Saccharomyces cerevisiae. Here, we deleted MgATG9, the orthologue of ScATG9, via targeted gene replacement in the phytopathogenic filamentous fungus Magnaporthe oryzae, and then analyzed the cellular distribution pattern of EGFP-MgAtg9 in the Mgatg9Delta mutant. We detected an expression profile of multiple green dots in the conidial cell inoculated in rich media and in the appressoria differentiated from the conidia in H(2)O. Concurrent with the punctation, we found some fluorescent signals loca...
Source: Autophagy - June 29, 2009 Category: Cytology Authors: Dong B, Liu XH, Lu JP, Zhang FS, Gao HM, Wang HK, Lin FC Tags: Autophagy Source Type: journals

Nuclear membrane-derived autophagy, a novel process that participates in the presentation of endogenous viral antigens during HSV-1 infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Complex membrane trafficking events are involved in the regulation of antigen processing and presentation of both endogenous and exogenous antigens. While these processes were believed to involve mainly organelles along the endo/phagocytic and the biosynthetic pathways, recent studies have shown that autophagy also participates actively in both innate and adaptive immunity. We have shown recently that, in macrophages infected with the Herpes simplex type 1 virus, autophagy plays a key role in the targeting of viral proteins to hydrolytic compartments, and their processing for presentation on MHC class I molecules. This...
Source: Autophagy - June 29, 2009 Category: Cytology Authors: English L, Chemali M, Desjardins M Tags: Autophagy Source Type: journals

The prognostic role of beclin 1 protein expression in high-grade gliomas.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
High-grade gliomas (HGG) have a poor outcome, however, prognostic subgroups of patients may be individuated by some clinico-biological parameters. It was recently demonstrated that the main response of HGG to therapy is autophagic death. Autophagy is involved in tumor suppression, and is defective in HGG, in which we previously found an underexpression of beclin 1 autophagic gene protein product. Underexpression of Beclin 1 protein has been correlated to poor patient outcome in other tumor types. In this paper, the prognostic role of Beclin 1 expression in HGG patients was investigated. We first evaluated the tumor cel...
Source: Autophagy - June 29, 2009 Category: Cytology Authors: Pirtoli L, Cevenini G, Tini P, Vannini M, Oliveri G, Marsili S, Mourmouras V, Rubino G, Miracco C Tags: Autophagy Source Type: journals

Autophagy of whole and partial chloroplasts in individually darkened leaves: A unique system in plants?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chloroplasts are the characteristic organelle of photoautotrophs. To acquire carbohydrates, the majority of leaf nitrogen is distributed to chloroplasts as photosynthetic proteins. During age-related senescence or under starvation conditions, chloroplasts become a major source of carbon and nitrogen for recycling. While bulk degradation of the cytosol and organelles must occur by autophagy in plants, the role of autophagy in chloroplast degradation is still unclear. Our recent results confirm the role of autophagy in both partial and whole chloroplast degradation, at least during promoted senescence of individually-dar...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Ishida H, Wada S Tags: Autophagy Source Type: journals

Implications of autophagy in anthrax pathogenicity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The etiological agent for anthrax is Bacillus anthracis, which produces lethal toxin (LT) that exerts a myriad of effects on many immune cells. In our previous study, it was demonstrated that LT and protective antigen (PA) induce autophagy in mammalian cells. Preliminary results suggest that autophagy may function as a cellular defense mechanism against LT-mediated toxemia. This degradation pathway may also be relevant to other aspects of the immune response in both innate and adaptive immunity. Understanding the role of autophagy in response to anthrax infection and the possibility of modulating this degradation pathw...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Tan YK, Vu HA, Kusuma CM, Wu A Tags: Autophagy Source Type: journals

NBR1 cooperates with p62 in selective autophagy of ubiquitinated targets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Selective degradation of intracellular targets, such as misfolded proteins and damaged organelles, is an important homeostatic function that autophagy has acquired in addition to its more general role in restoring the nutrient balance during stress and starvation. Although the exact mechanism underlying selection of autophagic substrates is not known, ubiquitination is a candidate signal for autophagic degradation of misfolded and aggregated proteins. p62/SQSTM1 was the first protein shown to bind both target-associated ubiquitin (Ub) and LC3 conjugated to the phagophore membrane, thereby effectively acting as an autop...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Kirkin V, Lamark T, Johansen T, Dikic I Tags: Autophagy Source Type: journals

Evolution of Atg1 function and regulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The serine/threonine kinase Atg1 plays an essential role downstream of TOR for the regulation of autophagy. In yeast, where Atg1 was first identified, a complex regulatory mechanism has been described that includes at least seven other interacting proteins and a phosphorylation-dependent switch. Recent findings confirm that the mammalian Atg1 homologues ULK1 and 2 have autophagy regulatory roles. However, we and others have also demonstrated mechanistic differences with the yeast model and between these two Atg1 family members. Here, we elaborate on our growing understanding of Atg1 function, incorporating findings fro...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Chan EY, Tooze SA Tags: Autophagy Source Type: journals

PCD and autophagy in the unicellular green alga Micrasterias denticulata.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Programmed cell death (PCD) plays a central role in normal plant development and is also induced by various biotic and abiotic stress factors. In the unicellular freshwater green alga Micrasterias denticulata morphological and biochemical hallmarks such as the appearance of autophagosomes, increased production of ROS and degradation of genomic DNA into small fragments ("DNA laddering") indicate PCD. Our data not only demonstrate that Micrasterias is capable of performing PCD under salt stress, but also that it is triggered by the ionic and not osmotic component of salinity. Additionally, results from the present and pr...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Affenzeller MJ, Darehshouri A, Andosch A, Lütz C, Lütz-Meindl U Tags: Autophagy Source Type: journals

Cancer cell death by design: Apoptosis, autophagy and glioma virotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy has been defined as a mechanism by which oncolytic adenoviruses mediate cell killing in some cancers, including malignant glioma. Until recently, however, adenovirus replication was regarded as a process that induced classical apoptosis in the infected cell. We have assessed the method of conditionally replicating adenovirus (CRAd) death in a model of malignant glioma, considering both autophagy and apoptosis as possible mechanisms of virally-induced cell death. Our initial investigations indicated that autophagy was the predominant system in CRAd-induced cell death in glioma. This appeared to be the case in ...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Tyler MA, Ulasov IV, Lesniak MS Tags: Autophagy Source Type: journals

p65/RelA binds and activates the beclin 1 promoter.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We unveiled novel p65/RelA consensus sites in the promoter of the beclin 1 gene and demonstrate that p65/RelA positively modulates canonical autophagy in various human cell lines both under basal conditions and upon induction by ceramide. Interestingly, we find that T cell receptor-dependent activation of Jurkat cells triggers an increase in the binding of p65/RelA to the beclin 1 promoter accompanied by enhanced autophagy, suggesting that p65/RelA could regulate T-cell activation and homeostasis through autophagy. PMID: 19458474 [PubMed - as supplied by publisher] (Source: Autophagy)
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Copetti T, Demarchi F, Schneider C Tags: Autophagy Source Type: journals

Gangliosides' protection against lysosomal pathology of synucleinopathies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Gangliosides are abundantly expressed in the nervous system, and deregulated expression or activity of gangliosides is associated with the progression of various disorders, including lysosomal storage diseases, Guillain-Barre syndrome and Alzheimer disease. By contrast, previous studies show that GM1 ganglioside may act in a protective manner in the drug (e.g., MPTP and 6-OHDA)-induced Parkinsonian models, although the precise mechanisms have not been well addressed. In our recent publication, dementia with Lewy bodies (DLB)-linked neuroblastoma cells were treated with D-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-pr...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Wei J, Fujita M, Sekigawa A, Sekiyama K, Waragai M, Hashimoto M Tags: Autophagy Source Type: journals

Autophagy is required for extension of yeast chronological life span by rapamycin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report herein that low concentrations of rapamycin stimulate macroautophagy during chronological aging and extend CLS. PMID: 19458476 [PubMed - as supplied by publisher] (Source: Autophagy)
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Alvers AL, Wood MS, Hu D, Kaywell AC, Dunn WA, Aris JP Tags: Autophagy Source Type: journals

A novel link between autophagy and the ubiquitin-proteasome system.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy and the ubiquitin-proteasome system (UPS) are the major routes for intracellular protein degradation. These two pathways were previously thought to be largely distinct. Here we summarize our recent work that demonstrates that long-term autophagy inhibition slows the clearance of short-lived UPS-specific substrates, like p53. This is caused by the accumulation of p62 after autophagy inhibition. These data suggest that the ramifications of a block in autophagy may be much wider than what was previously thought. Rather than simply decreasing clearance of autophagic substrates, while UPS flux is undisturbed, the ...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Korolchuk VI, Menzies FM, Rubinsztein DC Tags: Autophagy Source Type: journals

Impaired autophagosome-lysosome fusion in the pathogenesis of pancreatitis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In contrast to apoptosis, necrosis is generally viewed as a pro-inflammatory cell death mechanism. Accumulation of autophagosomes and massive acinar cell necrosis is observed in human acute pancreatitis, a severe and potentially lethal inflammatory condition. We have investigated the incidence of apoptosis, autophagy and necrosis affecting acinar cells in a rat model of acute pancreatitis induced by chronic alcohol intake and acute endotoxemia. We have observed that the combination of alcohol exposure and endotoxemia results in substantial accumulation of autophagosomes without an increase in autolysosomes, coupled to ...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Fortunato F, Kroemer G Tags: Autophagy Source Type: journals

Autophagy in protists: Examples of secondary loss, lineage-specific innovations, and the conundrum of remodeling a single mitochondrion.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy describes the process by which eukaryotes selectively and nonselectively target cytoplasm and entire organelles for lysosomal or (in yeast) vacuolar degradation. More than 30 different proteins contribute to this complex process, and it is widely recognized that the term autophagy does not describe merely a single linear pathway by which intracellular components are routed for lysosomal degradation. Yet, while autophagy has been unequivocally demonstrated in evolutionarily diverse organisms and the importance of autophagy in many aspects of human health and development is becoming ever more apparent, the exte...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Rigden DJ, Michels PA, Ginger ML Tags: Autophagy Source Type: journals

Lipases in lysosomes, what for?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19502773 [PubMed - as supplied by publisher] (Source: Autophagy)
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Czaja MJ, Cuervo AM Tags: Autophagy Source Type: journals

Identification of autophagy genes in Ciona intestinalis: A new experimental model to study autophagy mechanism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Programmed cell death (PCD) is a mechanism implicated in many physiological and pathological processes. Until recently, apoptosis (self-killing) was the most largely studied mechanism of PCD but a growing number of laboratories is now interested in autophagy (self-eating). In the past few years data showing a tight link between both pathways has accumulated. Until now our laboratory used Ciona intestinalis, a chordate model in which in vivo experiments are possible, to study apoptosis. Recently, we showed that autophagy also occurs in the development of Ciona intestinalis and that the specific markers of both types of ...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Godefroy N, Hoa C, Tsokanos F, Le Goff E, Douzery EJ, Baghdiguian S, Martinand-Mari C Tags: Autophagy Source Type: journals

Autophagy activation by NFkappaB is essential for cell survival after heat shock.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we analyze the consequences of NFkappaB activation during heat shock recovery, by comparing the heat shock response of NFkappaB competent and incompetent (p65/RelA-depleted) cells. We demonstrate for the first time that NFkappaB plays a major and crucial role during the heat shock response by activating autophagy, which increases survival of heat-treated cells. Indeed, we observed that autophagy is not activated during heat shock recovery and cell death is strongly increased in NFkappaB incompetent cells. Moreover, if autophagy is artificially induced in these cells, the cytotoxicity of heat shock is turned ...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Nivon M, Richet E, Codogno P, Arrigo AP, Kretz-Remy C Tags: Autophagy Source Type: journals

The essential role of early endosomes in autophagy is revealed by loss of COPI function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19502778 [PubMed - as supplied by publisher] (Source: Autophagy)
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Tooze SA, Razi M Tags: Autophagy Source Type: journals

Glutathione participates in the regulation of mitophagy in yeast.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The term mitophagy refers to the selective removal of mitochondria by autophagy. This process is very active in lactate-grown yeast cells during nitrogen starvation. Among different antioxidants tested, only N-acetyl L-cysteine (NAC) prevents mitophagy in lactate-grown nitrogen-starved cells and its effect is not related to its scavenging properties, but rather to the fueling effect of the glutathione pool. In these conditions, glutathione regulates mitophagy independently of general autophagy. PMID: 19502807 [PubMed - as supplied by publisher] (Source: Autophagy)
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Kiššová IB, Camougrand N Tags: Autophagy Source Type: journals

Viruses and arrested autophagosome development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is acknowledged as an important cellular defense mechanism against intracellular pathogens. As with other innate immune responses, pathogens have adapted to evade autophagy and in some cases, subvert the pathway to promote their own replication. Poliovirus, a prototypical small positive-strand RNA virus that replicates and assembles in the cytoplasm of the host cell, utilizes membranes derived from the autophagic pathway to aid viral replication and egress from the cell. Recently we made the surprising discovery that GFP-LC3-staining vesicles are physically immobilized during poliovirus infection. Here we dis...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Taylor MP, Jackson WT Tags: Autophagy Source Type: journals

Why doesn't Beclin 1, a BH3-only protein, suppress the anti-apoptotic function of Bcl-2?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Beclin 1 binds to Bcl-2 through its BH3 domain and this interaction inhibits starvation-induced autophagy. However, we have found that when Beclin 1 binds thus to Bcl-2, it fails to inhibit Bcl-2-mediated protection against four different inducers of apoptosis. In this punctum, we discuss possible reasons why Beclin 1 fails to behave like other BH3-only proteins and induce apoptosis. PMID: 19535901 [PubMed - as supplied by publisher] (Source: Autophagy)
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Ciechomska IA, Goemans CG, Tolkovsky AM Tags: Autophagy Source Type: journals

Building complex biological networks based upon model organisms: Mapping the human autophagy interactome via a hybrid yeast-human protein interaction network.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19535904 [PubMed - as supplied by publisher] (Source: Autophagy)
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Huett A, Xavier R Tags: Autophagy Source Type: journals

A cathepsin L-specific inhibitor preferentially inhibits degradation of autophagosomal LC3 and GABARAP in HeLa and Huh-7 cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CAA0225 ((2S,3S)-oxirane-2,3-dicarboxylic acid 2-[((S)-1-benzylcarbamoyl-2-phenyl-ethyl)-amide] 3-{[2-(4-hydroxy-phenyl)-ethyl]-amide}) is a cathepsin L-specific inhibitor recently selected out by extensive screening of a series of new epoxysuccinyl peptides. CAA0225 inhibited rat liver cathepsin L with IC(50) values of 1.9 nM, but not rat liver cathepsin B (IC(50), >1,000-5,000 nM). We compared effects of CAA0225 on autophagy with those of CA-074 that was previously developed as a cathepsin B-specific inhibitor. In HeLa and Huh-7 cells cultured under nutrient-deprived conditions both CAA0225 and CA-074 significantl...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Ueno T, Takahashi K Tags: Autophagy Source Type: journals

Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report here that microRNAs (miRNAs), a class of endogenous, 22-24 nucleotide noncoding RNA molecules able to affect stability and translation of mRNA, may represent a previously unrecognized mechanism for regulating beclin 1 expression and autophagy. We demonstrated that beclin 1 is a potential target for miRNA miR-30a, and this miRNA could negatively regulate beclin 1 expression resulting in decreased autophagic activity. Treatment of tumor cells with the miR-30a mimic decreased, and with the antagomir increased, the expression of beclin 1 mRNA and protein. Dual luciferase reporter assay confirmed that the miR-30a bind...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Zhu H, Wu H, Liu X, Li B, Chen Y, Ren X, Liu CG, Yang JM Tags: Autophagy Source Type: journals

NADPH oxidases contribute to autophagy regulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Reactive oxygen species (ROS) are emerging as regulators of autophagy in various cellular contexts. There are many cellular sources of ROS in eukaryotic cells. In phagocytes, the critical immune cells for host defense, the Nox2 NADPH oxidase generates ROS during phagocytosis and plays a central role in microbial killing. Toll-like receptors (TLRs) are important membrane microbial sensing receptors, which can activate Nox2,(1) and were recently demonstrated to signal autophagy targeting of phagosomes to promote their maturation.(2) Our recent study reveals that Nox2 activity and its generated ROS are key signals that in...
Source: Autophagy - June 27, 2009 Category: Cytology Authors: Huang J, Brumell JH Tags: Autophagy Source Type: journals