RRC ID 45657
Author Xie M, Roy R.
Title The Causative Gene in Chanarian Dorfman Syndrome Regulates Lipid Droplet Homeostasis in C. elegans.
Journal PLoS Genet
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.
Volume 11(6)
Pages e1005284
Published 2015-6-1
DOI 10.1371/journal.pgen.1005284
PMID 26083785
PMC PMC4470697
MeSH 1-Acylglycerol-3-Phosphate O-Acyltransferase / genetics* 1-Acylglycerol-3-Phosphate O-Acyltransferase / metabolism Amino Acid Sequence Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Fatty Acids, Unsaturated / metabolism Homeostasis Ichthyosiform Erythroderma, Congenital / genetics* Lipase / genetics Lipase / metabolism Lipid Droplets / metabolism* Lipid Metabolism, Inborn Errors / genetics* Molecular Sequence Data Muscular Diseases / genetics*
IF 5.175
Times Cited 12
C.elegans tm1944