title: AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA.
abstract: Lipids stored in lipid droplets are hydrolyzed via either cytosolic lipases or a selective form of macroautophagy known as lipophagy. We recently demonstrated that chaperone-mediated autophagy (CMA) is required for the initiation of lipolysis by either of these independent lipolytic pathways. CMA selectively degrades the lipid droplet proteins perilipins (PLIN) 2 and 3 from the lipid droplet surface, thus, facilitating the recruitment of cytosolic lipases and autophagy effector proteins to the lipid droplets. PLIN2 phosphorylation was observed upon induction of lipolysis, but the phosphorylating kinase and the relation of this phosphorylation with CMA of PLIN2 remained unknown. Here, we report that phosphorylation of PLIN2 is dependent on AMPK and occurs after the interaction of PLIN2 with the CMA chaperone HSPA8/Hsc70. Our results highlight a role for posttranslational modifications in priming proteins to be amenable for degradation by CMA.
authors.affiliation: a Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine , Bronx , NY USA.
authors.forename: Susmita
authors.initials: S
authors.lastname: Kaushik
authors.affiliation: a Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine , Bronx , NY USA.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Cuervo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D066292:Lipid Droplets / Q000187:drug effects / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D041681:NIH 3T3 Cells; D000070780:Perilipin-2 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects
chemical_list: D018832:Molecular Chaperones; D000070780:Perilipin-2; D047428:Protein Kinase Inhibitors; D055372:AMP-Activated Protein Kinases
keywords: chaperones; lipid droplets; lysosome-associated membrane protein 2A; lysosomes; perilipins; protein degradation