Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation

被引:232
作者
Kang, Chanhee [1 ]
You, Young-Jai [1 ]
Avery, Leon [1 ]
机构
[1] Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA
关键词
autophagy; muscarinic acetylcholine receptor signaling; starvation;
D O I
10.1101/gad.1573107
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Autophagy is a major pathway used to degrade long-lived proteins and organelles. Autophagy is thought to promote both cell and organism survival by providing fundamental building blocks to maintain energy homeostasis during starvation. Under different conditions, however, autophagy may instead act to promote cell death through an autophagic cell death pathway distinct from apoptosis. Although several recent papers suggest that autophagy plays a role in cell death, it is not known whether autophagy can cause the death of an organism. Furthermore, why autophagy acts in some instances to promote survival but in others to promote death is poorly understood. Here we show that physiological levels of autophagy act to promote survival in Caenorhabditis elegans during starvation, whereas insufficient or excessive levels of autophagy contribute to death. We found that inhibition of autophagy decreases survival of wild-type worms during starvation, and that muscarinic signaling regulates starvation-induced autophagy, at least in part, through the death-associated protein kinase signaling pathway. Furthermore, we found that in gpb-2 mutants, in which muscarinic signaling cannot be down-regulated, starvation induces excessive autophagy in pharyngeal muscles, which in turn, causes damage that may contribute to death. Taken together, our results demonstrate that autophagy can have either prosurvival or prodeath functions in an organism, depending on its level of activation.
引用
收藏
页码:2161 / 2171
页数:11
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