Circadian Control of DRP1 Activity Regulates Mitochondrial Dynamics and Bioenergetics

Cell Metab. 2018 Mar 6;27(3):657-666.e5. doi: 10.1016/j.cmet.2018.01.011. Epub 2018 Feb 22.


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.

Keywords: DRP1; bioenergetics; circadian clock; dynamics; fission; fusion; glycolysis; metabolism; mitochondria; oxidative phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Clocks*
  • Dynamins / metabolism*
  • Energy Metabolism
  • Fibroblasts / metabolism*
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics
  • Mitochondrial Proteins / metabolism
  • Tumor Cells, Cultured


  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • DNM1L protein, human
  • Dnm1l protein, mouse
  • Dynamins