title: Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress.
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 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.
authors.affiliation: Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Erin Quan
authors.initials: EQ
authors.lastname: Toyama
authors.affiliation: Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Herzig
authors.affiliation: Department of Neuroscience, Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA.
authors.forename: Julien
authors.initials: J
authors.lastname: Courchet
authors.affiliation: Department of Neuroscience, Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA.
authors.forename: Tommy L
authors.initials: TL
authors.lastname: Lewis
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Losón
authors.affiliation: Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Hellberg
authors.affiliation: Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Young
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Hsiuchen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neuroscience, Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA.
authors.forename: Franck
authors.initials: F
authors.lastname: Polleux
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Chan
authors.affiliation: Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Reuben J
authors.initials: RJ
authors.lastname: Shaw
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000201:enzymology; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000494:pharmacology; D034281:Dynamins; D004734:Energy Metabolism; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D012402:Rotenone / Q000494:pharmacology; D013312:Stress, Physiological
chemical_list: D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D012402:Rotenone; C030013:cactinomycin; D003609:Dactinomycin; D000249:Adenosine Monophosphate; D055372:AMP-Activated Protein Kinases; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins
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