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. Eckert, Anne 2018-03-06 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. application/pdf https://folia.unifr.ch/global/documents/306445 https://folia.unifr.ch/documents/306445/files/alb_ccd.pdf https://folia.unifr.ch/documents/306445/files/alb_cdd_sm.pdf https://folia.unifr.ch/documents/306445/files/alb_cdd_sm2.txt eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cmet.2018.01.011 info:eu-repo/semantics/openAccess License undefined Cell Metabolism. - 2018, vol. 27, no. 3, p. 657-666.e5 info:eu-repo/classification/udc/57 Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics http://purl.org/coar/resource_type/c_6501