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PMID:19416714

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Citation

Jo, H, Shim, J, Lee, JH, Lee, J and Kim, JB (2009) IRE-1 and HSP-4 contribute to energy homeostasis via fasting-induced lipases in C. elegans. Cell Metab. 9:440-8

Abstract

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.

Links

PubMed Online version:10.1016/j.cmet.2009.04.004

Keywords

Animals; Caenorhabditis elegans/enzymology; Caenorhabditis elegans Proteins/metabolism; Endoplasmic Reticulum/metabolism; Energy Metabolism; Fasting; Heat-Shock Proteins/metabolism; Lipase/classification; Lipase/metabolism; Phylogeny; Protein-Serine-Threonine Kinases/metabolism; RNA Interference

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:Q22060

enables

GO:0016298: lipase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:Q22060

involved_in

GO:0016042: lipid catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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