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Circadian Control of Mitochondrial Dynamics and Its Implication in Aging

Part of the Healthy Ageing and Longevity book series (HAL,volume 7)

Abstract

The circadian clock promotes metabolic efficiency by pre-programmed regulation of metabolic pathways in anticipation of the upcoming feeding/fasting cycle. Recent studies have suggested that the master circadian regulators Bmal1/Clock play an important role in controlling mitochondrial function, including oxidative metabolism and mitochondrial dynamics . The latter includes mitochondrial fusion, fission, and selective autophagy (mitophagy ) that follows fission. These processes not only allow mitochondria to undergo architectural/organizational changes in response to different nutrient conditions but also ensure quality control by removing damaged components through mitophagy . Results from mouse genetic models indicate that Bmal1-dependent regulation of fission and mitophagy genes reduces oxidative stress and maintains metabolic flexibility in the liver. In addition, aha-1, a C. elegans Bmal1 homologue, is required for orderly organizations of muscle mitochondria. Interestingly, Baml1 whole body knockout mice develop premature aging phenotypes, while AHA-1 over-expression increases lifespan in worms. Given that mitochondrial dysfunction appears to be a common feature associated with aging, obesity , and related metabolic diseases , these findings implicate an evolutionarily conserved regulatory mechanism that links mitochondrial fidelity to lifespan and/or healthspan.

Keywords

  • Mitochondrial dynamics
  • Mitophagy
  • Metabolic diseases
  • Oxidative stress
  • Electron transport chain
  • Circadian rhythm

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Fig. 7.1
Fig. 7.2
Fig. 7.3

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Acknowledgements

D. Jacobi and F. Atger are supported by the INSERM ATIP-Avenir program and by a grant from the Genavie foundation. C-.H. Lee is supported by American Diabetes Association grant 1-14-BS-122, American Heart Association grant 16GRNT31460005, and NIH grant R01DK113791.

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Correspondence to Chih-Hao Lee .

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Jacobi, D., Atger, F., Lee, CH. (2017). Circadian Control of Mitochondrial Dynamics and Its Implication in Aging. In: Jazwinski, S., Belancio, V., Hill, S. (eds) Circadian Rhythms and Their Impact on Aging. Healthy Ageing and Longevity, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-319-64543-8_7

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