ArticleNature metabolism2024
S-acylation of ATGL is required for lipid droplet homoeostasis in hepatocytes.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Cloning, expression, tertiary structure, activity characteristics, design of inhibitor, hydrolysis and inhibition mechanisms analysis of carp adipose triglyceride lipase (ATGL).Food chemistry. Molecular sciences · 2026Article
- Intracellular lipid droplets positively regulate the dormancy of colorectal cancer cells depending on ELF1-ACSL5 signaling.Journal of experimental & clinical cancer research : CR · 2026Article
- ZDHHC5: a pivotal palmitoyltransferase orchestrating signaling networks - unraveling mechanisms and therapeutic horizons.Biomarker research · 2026Review
- HOCl and viscosity dual-responsive fluorescent probe for accurate discrimination between early hepatocellular carcinoma and acute liver injury.Materials today. Bio · 2026Article
- OSBPL10 Drives Lipophagy-Mediated Lipid Mobilization to Promote Pancreatic Ductal Adenocarcinoma Progression.International journal of biological sciences · 2026Article
- Protein palmitoylation in hematological malignancies: mechanistic links to lipid metabolic reprogramming and therapy resistance.Frontiers in immunology · 2026Review
- Metabolomic Biomarkers for Non-Invasive Diagnosis of Coronary Artery Disease and Obstructive Sleep Apnea Co-Occurrence.Nature and science of sleep · 2026Article
- Protein S-acylation: Pathological mechanisms and novel therapeutic targets for diabetic complications.Chinese herbal medicines · 2026Review
- Lipid Droplet Dynamics in Alcoholic Steatohepatitis.The American journal of pathology · 2026Review
- GSK3β-Regulated Lipolysis is Required for Histone Acetylation and Decidualization in Early Pregnancy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Palmitoylation: an emerging therapeutic target bridging physiology and disease.Cellular & molecular biology letters · 2025Review
- Activation of Focal Adhesion Pathway byAnimals : an open access journal from MDPI · 2025Article
- Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.Innovation (Cambridge (Mass.)) · 2025Review
- CircABCA1 promotes ccRCC by reprogramming cholesterol metabolism and facilitating M2 macrophage polarization through IGF2BP3-mediated stabilization of SCARB1 mRNA.Molecular cancer · 2025Article
- Role of S-palmitoylation in digestive system diseases.Cell death discovery · 2025Review
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- Tools to Dissect Lipid Droplet Regulation, Players, and Mechanisms.ACS chemical biology · 2025Review
- Acetoacetate Ameliorates Hepatic Fibrosis by Targeting Peroxisome Proliferator-Activated Receptor Gamma to Restore Lipid Droplets in Activated Hepatic Stellate Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipid droplets (LDs) are organelles specialized in the storage of neutral lipids, cholesterol esters and triglycerides, thereby protecting cells from the toxicity of excess lipids while allowing for the mobilization of lipids in times of nutrient deprivation. Defects in LD function are associated with many diseases. S-acylation mediated by zDHHC acyltransferases modifies thousands of proteins, yet the physiological impact of this post-translational modification on individual proteins is poorly understood. Here, we show that zDHHC11 regulates LD catabolism by modifying adipose triacylglyceride lipase (ATGL), the rate-limiting enzyme of lipolysis, both in hepatocyte cultures and in mice. zDHHC11 S-acylates ATGL at cysteine 15. Preventing the S-acylation of ATGL renders it catalytically inactive despite proper localization. Overexpression of zDHHC11 reduces LD size, whereas its elimination enlarges LDs. Mutating ATGL cysteine 15 phenocopies zDHHC11 loss, causing LD accumulation, defective lipolysis and lipophagy. Our results reveal S-acylation as a mode of regulation of ATGL function and LD homoeostasis. Modulating this pathway may offer therapeutic potential for treating diseases linked to defective lipolysis, such as fatty liver disease.
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