Differential control of ATGL-mediated lipid droplet degradation by CGI-58 and G0S2.
Lipid droplets (LDs) are intracellular storage sites for triacylglyerols (TAGs)and steryl esters, and play essential roles in energy metabolism and membrane biosynthesis. Adipose triglyceride lipase (ATGL) is the key enzyme for TAG hydrolysis (lipolysis) in adipocytes and LD degradation in nonadipocyte cells. Lipase activity of ATGL in vivo largely depends on its C-terminal sequence as well as coactivation by CGI-58. Here we demonstrate that the C-terminal hydrophobic domain in ATGL is required for LD targeting and CGI-58-independent LD degradation. Overexpression of wild type ATGL causes a dramatic decrease in LD size and number, whereas a mutant lacking the hydrophobic domain fails to localize to LDs and to affect their morphology. Interestingly, coexpression of CGI-58 is able to promote LD turnover mediated by this ATGL mutant. Recently we have discovered that G0S2 acts as an inhibitor of ATGL activity and ATGL-mediated lipolysis. Here we show that G0S2 binds to ATGL irrelevantly of its activity state or the presence of CGI-58. In G0S2-expressing cells, the combined expression of CGI-58 and ATGL is incapable of stimulating LD turnover. We propose that CGI-58 and G0S2 regulate ATGL via non-competing mechanisms.
Lu
Xin
X
Department of Pediatrics and the Kentucky Pediatric Research Institute, University of Kentucky, Lexington, KY, USA.
Yang
Xingyuan
X
Liu
Jun
J
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008049:Lipase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000217:Acyltransferases
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D018797:Cell Cycle Proteins; D008049:Lipase; D034741:RNA, Small Interfering; C508073:G0S2 protein, human; C439972:ABHD5 protein, human; C494794:PNPLA2 protein, human; D000217:Acyltransferases