Mitochondrial dysfunction activates the AMPK signaling and autophagy to promote cell survival

查看全文 作　　者：Baozhong [1]Zhao;Lei [1]Qiang;Joy [2]Joseph;Balaraman [2]Kalyanaraman;Benoit [3]Viollet;Yu-Ying [1]He

机构地区：[1]Department of Medicine,Section of Dermatology,University of Chicago,Chicago,IL,USA;[2]Free Radical Research Center,Medical College of Wisconsin,Milwaukee,WI,USA;[3]INSERM U567,CNRS UMR8104,Department of Endocrinology,Metabolism and Cancer,Institut Cochin,Universite´Paris 5,75014 Paris,France

出　　处：《Genes & Diseases》索引2016年第3卷第1期,共6页

基　　金：This work was supported by the NIH/NIEHS grant ES024373 and ES016936(YYH);the American Cancer Society(ACS)grant RSG-13-078-01(YYH);the University of Chicago Cancer Research Center(P30 CA014599),the CTSA(UL1 TR000430);the University of Chicago Friends of Dermatology Endowment Fund. 摘　　要：Autophagy is a cellular self-eating process essential for stress response and maintainingtissue homeostasis by lysosomal degradation of unwanted or damaged proteins and organelles.Here, we show that cells with defective mitochondria induce autophagy to promotecell survival through activating the AMPK pathway. Loss of mitochondrial complex III proteincytochrome b activates the AMPK signaling and induced autophagy. Inhibiting mitochondria energeticsby mitochondria-targeted agents activates the AMPK signaling and induced autophagy.Genetic inhibition of AMPK inhibits autophagy induction in cells with defective mitochondria,while genetic inhibition of autophagy has no effect on AMPK activation. Mitochondria dysfunctionhas no effect of DNA repair of UV-induced DNA damage. However, mitochondria dysfunctionsensitizes cells to apoptosis induced by UV radiation. Genetic inhibition of autophagy orAMPK sensitized cells to apoptosis in cells with defective mitochondria. Our results demonstratethat AMPK and autophagy senses mitochondria dysfunction and serves as a mechanismfor survival. Our findings may provide new insights into the interplay between mitochondriafunction and autophagy process in maintaining tissue homeostasis, and suggest that this interactionmay play important roles in diseases such as cancer and neurodegeneration. 关键词：AMPK APOPTOSIS AUTOPHAGY DNA repair MITOCHONDRIA Ultraviolet radiation UV

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Mitochondrial dysfunction activates the AMPK signaling and autophagy to promote cell survival

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