Cellular energy metabolism also follows the rhythm of the circadian clock. A University of Basel study has now shown exactly how this works by revealing the relationship between the circadian rhythm and the mitochondrial network for the first time.
Countless genetically controlled clocks tick inside different parts of our bodies, such as the liver, kidneys and heart. Among other things, they initiate many metabolic processes, ensuring that these occur at the optimal time of day.
Mitochondria – small organelles that exist in almost all our cells and supply them with energy – play an important role in these cellular processes. Until now, it was unclear how exactly the 24-hour circadian rhythm regulated energy metabolism.
Fission protein sets the rhythm
In most cells, mitochondria connect in a constantly changing network that can adapt to various conditions. Mitochondria can thus fuse together and then divide again. Disruption of this fission-fusion dynamic can lead to health problems.
Researchers have now investigated exactly how the mitochondrial network interacts with our internal biological clock by using a combination of in vitro models and clock-deficient mice or mice with impaired mitochondrial fission.
Their results show that the mitochondrial fission-fusion cycle is controlled by the fission protein Drp1, which is in turn synchronized by an internal biological clock. This rhythm is integral to determining when and how much energy the mitochondria can supply.
“The time of day determines the design of the mitochondrial network, and this, in turn, influences the cells’ energy capacity,” explains study leader Professor Anne Eckert from the University of Basel’s Transfaculty Research Platform Molecular and Cognitive Neurosciences MCN.
Relationship between circadian clock and energy production
The researchers also showed that the mitochondrial network loses its rhythm if the circadian clock is impaired, which causes a decline in energy production in the cells.
Similarly, pharmacologically or genetically impairing the Drp1 fission protein upsets the energy production rhythm, which in turn affects the rhythm of the circadian clock.
These findings could play a role in the development of new therapeutic approaches; for example, for diseases that are characterized by an impaired circadian clock and compromised mitochondrial function, such as Alzheimer’s.
The study was published in the journal Cell Metabolism and involved researchers from the University of Basel, University of Zurich and University Psychiatric Clinics Basel (UPK Basel).
Karen Schmitt, Amandine Grimm, Robert Dallmann, Bjoern Oettinghaus, Lisa Michelle Restelli, Melissa Witzig, Naotada Ishihara, Katsuyoshi Mihara, Jürgen A. Ripperger, Urs Albrecht, Stephan Frank, Steven A. Brown, Anne Eckert
Circadian Control of DRP1 Activity Regulates Mitochondrial Dynamics and Bioenergetics
Cell Metabolism (2018), doi: 10.1016/j.cmet.2018.01.011
Prof. Dr. Anne Eckert, University of Basel, Transfaculty Research Platform Molecular and Cognitive Neurosciences / University Psychiatric Clinics Basel (UPK Basel), tel. +41 61 325 5487, e-mail: [email protected]
University of Basel