title: The Causative Gene in Chanarian Dorfman Syndrome Regulates Lipid Droplet Homeostasis in C. elegans.
abstract: AMP-activated kinase (AMPK) is a key regulator of many cellular mechanisms required for adjustment to various stresses induced by the changing environment. In C. elegans dauer larvae AMPK-null mutants expire prematurely due to hyperactive Adipose Triglyceride Lipase (ATGL-1) followed by rapid depletion of triglyceride stores. We found that the compromise of one of the three C. elegans orthologues of human cgi-58 significantly improves the survival of AMPK-deficient dauers. We also provide evidence that C. elegans CGI-58 acts as a co-activator of ATGL-1, while it also functions cooperatively to maintain regular lipid droplet structure. Surprisingly, we show that it also acts independently of ATGL-1 to restrict lipid droplet coalescence by altering the surface abundance and composition of long chain (C20) polyunsaturated fatty acids (PUFAs). Our data reveal a novel structural role of CGI-58 in maintaining lipid droplet homeostasis through its effects on droplet composition, morphology and lipid hydrolysis; a conserved function that may account for some of the ATGL-1-independent features unique to Chanarin-Dorfman Syndrome.
authors.affiliation: Department of Biology, McGill University, Penfield, Montreal, Quebec, Canada.
authors.forename: Meng
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Biology, McGill University, Penfield, Montreal, Quebec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Roy
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006706:Homeostasis; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics*; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism*; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D005231:Fatty Acids, Unsaturated; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C534632:ATGL-1 protein, C elegans; D008049:Lipase