Dissecting the Ca2+ dependence of DesA1 function in Mycobacterium tuberculosis
The desaturase DesA1 is an essential protein involved in the biosynthesis of mycolic acids, a class of lipids crucial to the structural maintenance of theMycobacterium tuberculosis cell wall. We demonstrate here that Ca2+-binding is critical to DesA1 function – disrupting this binding by mutating the Ca2+-binding site, leads to a defect in growth and compromises bacillary cell wall integrity. Mycobacterium tuberculosis (M. tb) has a complex cell wall, composed largely of mycolic acids, that are crucial to its structural maintenance. TheM. tb desaturase A1 (DesA1) is an essential Ca2+-binding protein that catalys...
Source: FEBS Letters - May 3, 2024 Category: Biochemistry Authors: Mamata Savanagouder,
Ravi Prasad Mukku,
Uday Kiran,
Chaitanya Veena Yeruva,
Nandhini Nagarajan,
Yogendra Sharma,
Tirumalai R. Raghunand Tags: Research Letter Source Type: research
CREB3 mediates the transcriptional regulation of PGC ‐1α, a master regulator of energy homeostasis and mitochondrial biogenesis
CREB3 is an endoplasmic reticulum stress-associated transcription factor that has recently been implicated in metabolic regulation due to the altered lipid accumulation phenotypes seen in CREB3-deficient mice. PGC-1 α is a master metabolic regulator of energy homeostasis and mitochondrial biogenesis. Here, we show that CREB3 regulates the expression ofPPARGC1A, which encodes PGC-1 α. The findings underline the potential role of CREB3 in energy metabolism. Lipid metabolism hinges on a balance between lipogenesis and fatty acid oxidation (FAO). Disruptions in this balance can induce endoplasmic reticulum (ER) stress trigge...
Source: FEBS Letters - May 3, 2024 Category: Biochemistry Authors: Briana Locke,
Elena Campbell,
Ray Lu Tags: Research Letter Source Type: research
Technological advancements in functional interpretation of genome ‐wide association studies (GWAS) findings: bridging the gap to clinical translation
Genome-wide association studies (GWAS) significantly advanced our understanding of the genetic underpinnings of diseases. However, challenges persist, particularly in interpreting non-coding variants in linkage disequilibrium that affect genes in disease-relevant cells. Addressing key obstacles —identifying causal variants, uncovering target genes, and understanding their network impact—is crucial. This graphical review navigates advanced techniques to fully leverage GWAS for future therapeutic breakthroughs. (Source: FEBS Letters)
Source: FEBS Letters - April 30, 2024 Category: Biochemistry Authors: Redouane Aherrahrou,
Minna U Kaikkonen Tags: Graphical Review Source Type: research
The role of ferroptosis as a regulator of oxidative stress in the pathogenesis of ischemic stroke
Cell death by ferroptosis results from disrupted iron metabolism, leading to redox-active Fenton reactions that generate lipid peroxidation. In ischemic stroke, where blood flow to the brain is limited, elevated iron absorption exacerbates oxidative stress, potentially inducing ferroptotic neuronal death. Studies demonstrate the involvement of ferroptosis in ischemic stroke, prompting exploration of ferroptosis-targeting therapies. Ferroptosis is a unique form of cell death that was first described in 2012 and plays a significant role in various diseases, including neurodegenerative conditions. It depends on a dysregulatio...
Source: FEBS Letters - April 27, 2024 Category: Biochemistry Authors: Susana Delgado ‐Martín,
Antonio Martínez‐Ruiz Tags: Review Source Type: research
Molecular determinants of lipid droplet subpopulations and their fates
Lipid droplets (LDs) are energy-rich organelles mobilized by lipolysis or micro-lipophagy in yeast. Here, we discuss how the LD proteins Ldo16/45 and Tld1 target to LD subsets and influence LD turnover. Tld1 and Ldo proteins mark LD subsets, and Tld1 inhibits lipolysis whereas Ldo1 proteins promote micro-lipophagy. Thus, Ldo and Tld proteins appear to dictate the fate of LD subsets in lipid turnover. Distinct pools of lipid droplets (LDs) exist in individual cells and are demarcated both by their unique proteomes and lipid compositions. Focusing on yeast-based work, we briefly review the state of understanding of LD subset...
Source: FEBS Letters - April 26, 2024 Category: Biochemistry Authors: W. Mike Henne Tags: In a Nutshell Source Type: research
Insights into conformational changes in cytochrome b during the early steps of its maturation
Structure prediction was used to generate models of early assembly intermediates of cytochromeb (Cytb), the central catalytic subunit of complex III in the mitochondrial respiratory chain. Structures of the first intermediates were validated by previous crosslinking data. The binding of Cytb to the assembly factor Cbp3-Cbp6 results in an open conformation that should facilitate the incorporation of its heme cofactors. Membrane proteins carrying redox cofactors are key subunits of respiratory chain complexes, yet the exact path of their folding and maturation remains poorly understood. Here, using cryo-EM and structure pred...
Source: FEBS Letters - April 26, 2024 Category: Biochemistry Authors: Andreas Carlstr öm,
Martin Ott Tags: Research Letter Source Type: research
Disrupting the interaction between a p53 gain ‐of‐function mutant and the transcriptional co‐activator PC4 reverses drug resistance in cancer cells
In a tumor cell harboring the gain-of-function mutant R273Hp53, the mutant p53 protein is recruited to the promoters of theMDR1 andUBE2C multidrug resistance-associated genes, assisted by the chromatin-associated protein PC4. This recruitment upregulates both genes. A peptide designed to disrupt the R273Hp53 –PC4 interaction, downregulatesMDR1 andUBE2C expression, sensitizing the cells to doxorubicin. This suggests that the PC4 –R273Hp53 interaction is a promising target for reducing drug resistance. PC4 is a chromatin-associated protein and transcriptional coactivator whose role in gene regulation by wild-type p53 is ...
Source: FEBS Letters - April 26, 2024 Category: Biochemistry Authors: Priya Mondal,
Kumar Singha Roy,
Supriya Varsha Bhagat,
Siddharth Singh,
Anupa Chattopadhyay,
Damayanti Das Ghosh,
Tapas K. Kundu,
Susanta Roychoudhury,
Siddhartha Roy Tags: Research Article Source Type: research
THAP3 recruits SMYD3 to OXPHOS genes and epigenetically promotes mitochondrial respiration in hepatocellular carcinoma
Through bioinformatic analysis of transcriptomes in the cancer genome atlas (TCGA), we identified a new role for the transcription factor THAP domain-containing 3 (THAP3) in the expression of oxidative phosphorylation (OXPHOS) genes and mitochondrial respiration. Mechanistically, THAP3 cooperated with the histone methyltransferase SET and MYND domain-containing protein 3 (SMYD3) to upregulate H3K4me3 and promote OXPHOS gene expression. These actions of THAP3 support liver cancer cell proliferation and contribute to tumor development. Mitochondria harbor the oxidative phosphorylation (OXPHOS) system to sustain cellular resp...
Source: FEBS Letters - April 26, 2024 Category: Biochemistry Authors: Zi ‐Hao Wang,
Jingyi Wang,
Fuchen Liu,
Sijun Sun,
Quan Zheng,
Xiaotian Hu,
Zihan Yin,
Chengmei Xie,
Haiyan Wang,
Tianshi Wang,
Shengjie Zhang,
Yi‐Ping Wang Tags: Research Article Source Type: research
Mitochondrial fractions located in the cytoplasmic and peridroplet areas of white adipocytes have distinct roles
White adipocytes contain two mitochondrial fractions: cytoplasmic mitochondria (CMw) and peridroplet mitochondria (PDMw). The formation of PDMw is partially regulated by perilipin 1 (PLIN1). CMw is responsible for β-oxidation, whereas PDMw is associated with diacylglycerol acyltransferase 2 (DGAT2) and contributes to the supply of triglycerides to lipid droplets. The role of mitochondria in white adipocytes (WAs) has not been fully explored. A recent study revealed that brown adipocytes contain functionally distinct mitochondrial fractions, cytoplasmic mitochondria, and peridroplet mitochondria. However, it is not known w...
Source: FEBS Letters - April 25, 2024 Category: Biochemistry Authors: Masayuki Fuwa,
Kazuo Kajita,
Ichiro Mori,
Motochika Asano,
Toshiko Kajita,
Takao Senda,
Takeshi Inagaki,
Hiroyuki Morita Tags: Research Article Source Type: research
Evidence for partial functional overlap of KEA and MSL transport proteins in the chloroplast inner envelope of Arabidopsis thaliana
Plant chloroplasts contain two independent ion export mechanisms from the KEA and the MSL family. Since it was unknown if these systems work in concert, we isolated a double loss-of-function mutant. The resulting plants exhibit distinct phenotypic deficits such as pale leaves, slow growth, and poor photosynthetic rates. This shows that chloroplast KEA and MSL functions overlap to some degree. Arabidopsis thaliana possesses two different ion-export mechanisms in the plastid inner envelope membrane. Due to a genome duplication, the transport proteins are encoded by partly redundant loci: K+-efflux antiporter1 (KEA1) and KEA2...
Source: FEBS Letters - April 25, 2024 Category: Biochemistry Authors: Carsten V ölkner,
Lorenz J. Holzner,
Katinka Bünger,
Beata Szulc,
Chance M. Lewis,
Andreas Klingl,
Hans‐Henning Kunz Tags: Research Letter Source Type: research
Structural and functional insights into the enzymatic activities of lipases from Burkholderia stagnalis and Burkholderia plantarii
In this study, we determined the crystal structure of BsL at 1.40 Å resolution. Utilizing structural insights, we have successfully augmented the interesterification activity of BpL by over twofold. This enhancement was achieved by substituting threonine with serine at position 289 through forming an expansive space in the substrate-binding site. Additionally, we discuss the activity mechanism based on the kinetic parameters. Our study sheds light on the structural determinants of the interesterification activity of lipase. (Source: FEBS Letters)
Source: FEBS Letters - April 25, 2024 Category: Biochemistry Authors: Saori Kataoka,
Sayuri Kawamoto,
Sayuri Kitagawa,
Wataru Kugimiya,
Kazunobu Tsumura,
Yukie Akutsu,
Tomomi Kubota,
Kazuhiko Ishikawa Tags: Research Article Source Type: research
Structural basis for the minimal bifunctional alginate epimerase AlgE3 from Azotobacter chroococcum
Alginate-modifying enzymes are promising for tailoring alginate for further applications in food additives, pharmaceuticals, and biomedical materials. Our work provided a structural basis for substrate binding of the bifunctional alginate epimerase AlgE3. Besides, the enzymatic activity profiles of AlgE3 combined with structural and hydrodynamic properties explained the preference for substrates with different chain lengths and requirement of calcium ions. Among the epimerases specific to alginate, some of them inAzotobacter genera convert β-d-mannuronic acid to α-l-guluronic acid but also have lyase activity to degrade ...
Source: FEBS Letters - April 23, 2024 Category: Biochemistry Authors: Takaaki Fujiwara,
Eriko Mano,
Eriko Nango Tags: Research Article Source Type: research
Selection of bifunctional RNAs with specificity for arginine and lipid membranes
Here, we constructed a bifunctional RNA 10Arg aptamer that is specific for arginine and lipids. The selection-amplification method yielded several RNA 10Arg(D) sequences with improved affinity for arginine and liposomes. Generation of these bispecific RNAs supports the hypothesis that an RNA molecule can bind both to RNA-binding proteins through arginine and to membrane lipid rafts, thus facilitating RNA loading into extracellular vesicles. The molecular mechanisms of selective RNA loading into exosomes and other extracellular vesicles are not yet completely understood. In order to show that a pool of RNA sequences binds b...
Source: FEBS Letters - April 23, 2024 Category: Biochemistry Authors: Teresa Janas,
Karolina Sapo ń,
Tadeusz Janas Tags: Research Article Source Type: research
Front Cover
Cover illustration Cryo-EM reconstruction of the Slo1 potassium channel bound by its auxiliary subunit γ1 which assists in bypassing voltage regulation. This figure refers to the article by Redhardtet al. (Source: FEBS Letters)
Source: FEBS Letters - April 22, 2024 Category: Biochemistry Tags: Issue Information Source Type: research
Deacylases —structure, function, and relationship to diseases
S-acylation is catalyzed by a group of acyltransferases, ZDHHCx, acting on various target proteins. The reverse reaction is mediated by protein acylases. The S-acylation-deacylation cycle controls the function of target proteins. Abnormal cycles can lead to various pathological conditions. Reversible S-acylation plays a pivotal role in various biological processes, modulating protein functions such as subcellular localization, protein stability/activity, and protein –protein interactions. These modifications are mediated by acyltransferases and deacylases, among which the most abundant modification is S-palmitoylation. G...
Source: FEBS Letters - April 22, 2024 Category: Biochemistry Authors: Shuxian Wang,
Xiaoke Xing,
Jialin Ma,
Sihao Zheng,
Qibin Song,
Pingfeng Zhang Tags: Review Source Type: research
