AMP-Activated Kinase Regulates Lipid Droplet Localization and Stability of Adipose Triglyceride Lipase in C. elegans Dauer Larvae

• DOI: 10.1371/journal.pone.0130480
• Publication Date: 2015-06-22T18:26:27Z
• Authors: Meng Xie; Richard Roy
• Keywords: Adipose triglyceride lipase; Lipid droplet; AMP-Activated Protein Kinase

Animals have developed diverse mechanisms to adapt their changing environment. Like many organisms the free-living nematode C. elegans can alternate between a reproductive mode or diapause-like "dauer" stage during larval development circumvent harsh environmental conditions. The master metabolic regulator AMP-activated protein kinase (AMPK) is critical for survival dauer stage, where it phosphorylates adipose triglyceride lipase (ATGL-1) at multiple sites block lipid hydrolysis and ultimately protect cellular triglyceride-based energy depot from rapid depletion. However, how AMPK-mediated phosphorylation affects function of ATGL-1 has not been characterised molecular level. Here we show that AMPK leads generation 14-3-3 binding on ATGL-1, which are recognized by orthologue PAR-5. Physical interaction with PAR-5 results in sequestration away droplets eventual proteasome-mediated degradation. In addition, also major site Ser 303, required both modification its droplet localization Our data provide mechanistic insight as functions enhance through ability accumulated deposits preserve stores periods extended duress.