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Mitochondrial dysfunction in metabolism and ageing: shared mechanisms and outcomes?

Abstract

Mitochondria are key in the metabolism of aerobic organisms and in ageing progression and age-related diseases. Mitochondria are essential for obtaining ATP from glucose and fatty acids but also in many other essential functions in cells including aminoacids metabolism, pyridine synthesis, phospholipid modifications and calcium regulation. On the other hand, the activity of mitochondria is also the principal source of reactive oxygen species in cells. Ageing and chronic age-related diseases are associated with the deregulation of cell metabolism and dysfunction of mitochondria. Cell metabolism is controlled by three major nutritional sensors: mTOR, AMPK and Sirtuins. These factors control mitochondrial biogenesis and dynamics by regulating fusion, fission and turnover through mito- and autophagy. A complex interaction between the activity of these nutritional sensors, mitochondrial biogenesis rate and dynamics exists and affect ageing, age-related diseases including metabolic disease. Further, mitochondria maintain a constant communication with nucleus modulating gene expression and modifying epigenetics. In this review we highlight the importance of mitochondria in ageing and the repercussion in the progression of age-related diseases and metabolic disease.

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Funding

The research group is funded by the Andalusian Government Grant BIO177 (FEDER funds of European Commission). Research has been funded by the Spanish Ministry of Economy and Competitiveness Grant DEP2012-39985 and Instituto de Salud Carlos III FIS Grant PI14/01962. Authors are also members of the CIBERER, Instituto Carlos III, of the Spanish Ministry of Health.

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Correspondence to Guillermo López-Lluch.

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López-Lluch, G., Hernández-Camacho, J.D., Fernández-Ayala, D.J.M. et al. Mitochondrial dysfunction in metabolism and ageing: shared mechanisms and outcomes?. Biogerontology 19, 461–480 (2018). https://doi.org/10.1007/s10522-018-9768-2

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  • DOI: https://doi.org/10.1007/s10522-018-9768-2

Keywords

  • Mitochondria
  • Metabolism
  • Ageing
  • Metabolic syndrome
  • Fat
  • Mitochondrial dynamics
  • ROS