Publication Date:
2016-01-28
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toyama, Erin Quan -- Herzig, Sebastien -- Courchet, Julien -- Lewis, Tommy L Jr -- Loson, Oliver C -- Hellberg, Kristina -- Young, Nathan P -- Chen, Hsiuchen -- Polleux, Franck -- Chan, David C -- Shaw, Reuben J -- K99 NS091526/NS/NINDS NIH HHS/ -- K99NS091526/NS/NINDS NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- R01CA172229/CA/NCI NIH HHS/ -- R01DK080425/DK/NIDDK NIH HHS/ -- R01GM062967/GM/NIGMS NIH HHS/ -- R01GM110039/GM/NIGMS NIH HHS/ -- R01NS089456/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):275-81. doi: 10.1126/science.aab4138.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ; Department of Neuroscience, Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA. ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. ; Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. shaw@salk.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816379" target="_blank"〉PubMed〈/a〉
Keywords:
AMP-Activated Protein Kinases/chemistry/genetics/*metabolism
;
Adenosine Monophosphate/metabolism
;
Amino Acid Motifs
;
Cell Line, Tumor
;
Cytoplasm/enzymology
;
Dactinomycin/analogs & derivatives/pharmacology
;
*Energy Metabolism
;
Enzyme Activation
;
GTP Phosphohydrolases/genetics/metabolism
;
Humans
;
Microtubule-Associated Proteins/genetics/metabolism
;
Mitochondria/drug effects/enzymology/*physiology
;
*Mitochondrial Dynamics
;
Mitochondrial Proteins/genetics/metabolism
;
Molecular Sequence Data
;
Rotenone/pharmacology
;
*Stress, Physiological
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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