IRE-1 and HSP-4 Contribute to Energy Homeostasis via Fasting-induced Lipases in C. elegans
IRE-1 and HSP-4 Contribute to Energy Homeostasis via Fasting-induced Lipases in C. elegans
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DOI：
10.1016/j.cmet.2009.04.004
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发表时间：
2009-05-06
期刊：
影响因子：
29
通讯作者：
Kim, Jae Bum
中科院分区：
文献类型：
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作者：
Jo, Hyunsun;Shim, Jiwon;Kim, Jae Bum
内质网（ER）是与脂质代谢相关的细胞器。然而，ER参与营养状态依赖的能量稳态在很大程度上是未知的。我们证明，IRE-1（一种已知参与未折叠蛋白反应的ER蛋白）和HSIP-4（一种ER伴侣蛋白）调节新型禁食诱导脂肪酶FIL-1和FIL-2的表达，这两种脂肪酶FIL-1和FIL-2在禁食时诱导脂肪颗粒水解C。优美的RNAi和异位表达实验表明，FIL-1和FIL-2是禁食诱导的脂肪颗粒分解的必要和充分条件。ire-1和hsp-4突变动物在饥饿期间不能水解脂肪颗粒，这损害了它们的运动能力，而补充葡萄糖可以挽救它们的运动能力，这暗示了ire-1/hsp-4依赖的脂解对于禁食期间储存脂肪的能量供应的重要性。这些数据表明，ER驻留蛋白IRE-1和HSP-4是关键的营养传感器，调节诱导型脂肪酶的表达，以维持全身能量稳态在C。优美的
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 HSIP-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.