Journal article

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Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics

  • Schmitt, Karen Neurobiology Lab for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular & Cognitive Neuroscience, University of Basel, Basel, Switzerland - Psychiatric University Clinics, University of Basel, Switzerland
  • Grimm, Amandine Neurobiology Lab for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular & Cognitive Neuroscience, University of Basel, Basel, Switzerland - Psychiatric University Clinics, University of Basel, Switzerland
  • Dallmann, Robert Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
  • Oettinghaus, Bjoern Division of Neuropathology, Institute of Pathology, University Hospital Basel, Switzerland
  • Restelli, Lisa Michelle Division of Neuropathology, Institute of Pathology, University Hospital Basel, Switzerland
  • Witzig, Melissa Neurobiology Lab for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular & Cognitive Neuroscience, University of Basel, Basel, Switzerland - Psychiatric University Clinics, University of Basel, Switzerland
  • Ishihara, Naotada Department of Protein Biochemistry, Institute of Life Science, Kurume University, Japan
  • Mihara, Katsuyoshi Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
  • Ripperger, Jürgen A. Department of Biology, Unit of Biochemistry, University of Fribourg, Switzerland
  • Albrecht, Urs Department of Biology, Unit of Biochemistry, University of Fribourg, Switzerland
  • Frank, Stephan Division of Neuropathology, Institute of Pathology, University Hospital Basel, Switzerland
  • Brown, Steven A. Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
  • Eckert, Anne Neurobiology Lab for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular & Cognitive Neuroscience, University of Basel, Basel, Switzerland - Psychiatric University Clinics, University of Basel, Switzerland
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    06.03.2018
Published in:
  • Cell Metabolism. - 2018, vol. 27, no. 3, p. 657-666.e5
English Mitochondrial fission-fusion dynamics and mitochondrial bioenergetics, including oxidative phosphorylation and generation of ATP, are strongly clock controlled. Here we show that these circadian oscillations depend on circadian modification of dynamin-related protein 1 (DRP1), a key mediator of mitochondrial fission. We used a combination of in vitro and in vivo models, including human skin fibroblasts and DRP1-deficient or clock-deficient mice, to show that these dynamics are clock controlled via circadian regulation of DRP1. Genetic or pharmacological abrogation of DRP1 activity abolished circadian network dynamics and mitochondrial respiratory activity and eliminated circadian ATP production. Pharmacological silencing of pathways regulating circadian metabolism and mitochondrial function (e.g., sirtuins, AMPK) also altered DRP1 phosphorylation, and abrogation of DRP1 activity impaired circadian function. Our findings provide new insight into the crosstalk between the mitochondrial network and circadian cycles.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/306445
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