AMP-activated protein kinase mediates mitochondrial fission in response to energy stress
By E. Q. Toyama, S. Herzig, J. Courchet, Tommy L. Lewis, O. Loson, Kristina Hellberg, N. Young, Hsiuchen Chen, F. Polleux, D. C. Chan and 1 more. Science, 2016
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How to shape mitochondrial networks Mitochondria undergo fragmentation or fusion in response to changes in cellular metabolism. Toyama et al. report that adenosine monophosphate-activated protein kinase (AMPK) is both necessary and sufficient to control mitochondrial fragmentation. AMPK functions as a sensor to monitor the energy status of the cell by phosphorylating mitochondrial fission factor (MFF), a protein of the mitochondrial outer membrane. MFF then acts to recruit a cytoplasmic guanosine triphosphatase that promotes mitochondrial fission. Science, this issue p. 275 An energy-sensing kinase phosphorylates a mitochondrial membrane protein that initiates fragmentation. 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.
Subfields: Epidemiology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/576d2c4ef0387ea56db4b80945e07b19e08417d2
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Citations in the corpus
- Mitochondrial dynamics in health and disease: mechanisms and potential targets (2023, background): “In addition, AMP-activated protein kinase (AMPK) phosphorylates Mff, then promote the binding of Drp1 with Mff, which facilitates recruitment of Drp1 from the cytosol to mitochondria under energetic stress.(47) Moreover, E3 ubiquitin ligase MARCH5 mediated-ubiquitination of Drp1 protein and its rece”
- Mitochondrial dysfunction in cell senescence and aging (2022, background): “AMPK activation promotes mitochondrial biogenesis and regulates mitochondrial dynamics and mitophagy (86), partially by promoting SIRT1-dependent PGC-1α deacetylation by increasing intracellular NAD+/NADH ratio (87).”
- AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control. (2020, background): “…(Egan et al., 2011b), and mitochondrial fission, perhaps via phosphorylation 394 of proteins involved in mitochondrial fission such as MFF (mitochondrial fission factor) or 395 MTFR1L (mitochondrial fission regulator-1-like) (Ducommun et al., 2015; Schaffer et al., 2015; 396 Toyama et al., 2016).”