AMP-activated protein kinase mediates mitochondrial fission in response to energy stress

Toyama, Erin Quan; Herzig, Sébastien; Courchet, Julien; Lewis, Tommy L.; Losón, Oliver C.; Hellberg, Kristina; Young, Nathan P.; Chen, Hsiuchen; Polleux, Franck; Chan, David C.; Shaw, Reuben J.

doi:10.1126/science.aab4138

articleScienceJan 14, 2016GREEN OA

AMP-activated protein kinase mediates mitochondrial fission in response to energy stress

EQErin Quan Toyama SHSébastien Herzig JCJulien Courchet TLTommy L. Lewis OCOliver C. Losón

Salk Institute for Biological Studies · Howard Hughes Medical Institute · +2 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

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…

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Topics & keywords

Topics

Keywords

Mitochondrial fission
AMPK
Cell biology
Mitochondrion
mitochondrial fusion
Mitochondrial DNA
DNAJA3
ATP–ADP translocase

UN Sustainable Development Goals

Affordable and clean energy

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