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Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics
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Schmitt, Karen, Grimm, Amandine, Dallmann, Robert, Oettinghaus, Bjoern, Restelli, Lisa Michelle, Witzig, Melissa, Ishihara, Naotada, Mihara, Katsuyoshi, Ripperger, Jürgen A., Albrecht, Urs, Frank, Stephan, Brown, Steven A. and Eckert, Anne (2018) Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metabolism, 27 (3). pp. 657-666. doi:10.1016/j.cmet.2018.01.011 ISSN 1550-4131.
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WRAP-circadian-control-DRP1-activity-regulates-mitochondrial-dynamics-bioenergetics-Dallman-2018.pdf - Accepted Version - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (4056Kb) |
Official URL: http://dx.doi.org/10.1016/j.cmet.2018.01.011
Abstract
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.
Item Type: | Journal Article | |||||||||||||||||||||||||||
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Subjects: | Q Science > QP Physiology | |||||||||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Circadian rhythms, Mitochondria, Bioenergetics, Glycolysis, Phosphorylation | |||||||||||||||||||||||||||
Journal or Publication Title: | Cell Metabolism | |||||||||||||||||||||||||||
Publisher: | Cell Press | |||||||||||||||||||||||||||
ISSN: | 1550-4131 | |||||||||||||||||||||||||||
Official Date: | 6 March 2018 | |||||||||||||||||||||||||||
Dates: |
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Volume: | 27 | |||||||||||||||||||||||||||
Number: | 3 | |||||||||||||||||||||||||||
Page Range: | pp. 657-666 | |||||||||||||||||||||||||||
DOI: | 10.1016/j.cmet.2018.01.011 | |||||||||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||||||||
Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||||||||
Date of first compliant deposit: | 2 March 2018 | |||||||||||||||||||||||||||
Date of first compliant Open Access: | 22 February 2019 | |||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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