线粒体分裂
安普克
线粒体融合
线粒体
线粒体DNA
细胞生物学
DNAJA3公司
ATP-ADP转位酶
化学
蛋白激酶A
生物
线粒体内膜
磷酸化
生物化学
基因
作者
Erin Quan Toyama,Sébastien Herzig,Julien Courchet,Tommy L. Lewis,Oliver C. Losón,Kristina Hellberg,Nathan P. Young,Hsiuchen Chen,Franck Polleux,David C. Chan,Reuben J. Shaw
出处
期刊:Science
[American Association for the Advancement of Science]
日期:2016-01-15
卷期号:351 (6270): 275-281
被引量:920
标识
DOI:10.1126/science.aab4138
摘要
Mitochondria undergo fragmentation in response to electron transport chain (ETC) poisons and mitochondrial DNA-linked disease mutations, yet how these stimuli mechanistically connect to the mitochondrial fission and fusion machinery is poorly understood. We found that the energy-sensing adenosine monophosphate (AMP)-activated protein kinase (AMPK) is genetically required for cells to undergo rapid mitochondrial fragmentation after treatment with ETC inhibitors. Moreover, direct pharmacological activation of AMPK was sufficient to rapidly promote mitochondrial fragmentation even in the absence of mitochondrial stress. A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission. Nonphosphorylatable and phosphomimetic alleles of the AMPK sites in MFF revealed that it is a key effector of AMPK-mediated mitochondrial fission.
科研通智能强力驱动
Strongly Powered by AbleSci AI