IRE-1 and HSP-4 contribute to energy homeostasis via fasting-induced lipases in C. elegans.
The endoplasmic reticulum (ER) is an organelle associated with lipid metabolism. However, the involvement of the ER in nutritional status-dependent energy homeostasis is largely unknown. We demonstrate that IRE-1, an ER protein known to be involved in the unfolded protein response, and HSP-4, an ER chaperone, regulate expression of the novel fasting-induced lipases FIL-1 and FIL-2, which induce fat granule hydrolysis upon fasting in C. elegans. RNAi and ectopic expression experiments demonstrated that FIL-1 and FIL-2 are both necessary and sufficient for fasting-induced fat granule breakdown. Failure of ire-1 and hsp-4 mutant animals to hydrolyze fat granules during starvation impaired their motility, which was rescued by glucose supplementation, implicating the importance of ire-1/hsp-4-dependent lipolysis for energy supply from stored fat during fasting. These data suggest that the ER-resident proteins IRE-1 and HSP-4 are key nutritional sensors that modulate expression of inducible lipases to maintain whole-body energy homeostasis in C. elegans.
Research Center for Functional Cellulomics, Department of Biological Sciences, Seoul National University, Seoul, Korea.
Hyunsun
H
Jo
Jiwon
J
Shim
Jung Hyun
JH
Lee
Junho
J
Lee
Jae Bum
JB
Kim
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004734:Energy Metabolism; D005215:Fasting; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008049:Lipase / Q000145:classification / Q000378:metabolism*; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference
D029742:Caenorhabditis elegans Proteins; D006360:Heat-Shock Proteins; C502196:Hsp-4 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C541905:IRE-1 protein, C elegans; D008049:Lipase