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Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging

Journal

Publisher

MDPI
DOI: 10.3390/ijms22158179

Keywords

skeletal muscle; mitochondrial dynamics; mitophagy; autophagy; aging; sarcopenia

Funding

  1. Natural Sciences and Engineering Council of Canada (NSERC) [RGPIN-2021-03724]
  2. Canadian Institutes of Health Research (CIHR) [MOP-93760, MOV-409262]
  3. FEDER [FIS 18/00075, FIS 21/00215]
  4. Spanish Ministry of Science and Innovation
  5. Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) 2020 (Spain)

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The maintenance of mitochondrial integrity is crucial for muscle health, with dysfunctional mitochondrial dynamics and mitophagy potentially contributing to sarcopenia. Enhancing mitophagy in skeletal muscle may be a promising therapeutic target to prevent or treat skeletal muscle dysfunction in the elderly.
The maintenance of mitochondrial integrity is critical for muscle health. Mitochondria, indeed, play vital roles in a wide range of cellular processes, including energy supply, Ca2+ homeostasis, retrograde signaling, cell death, and many others. All mitochondria-containing cells, including skeletal muscle cells, dispose of several pathways to maintain mitochondrial health, including mitochondrial biogenesis, mitochondrial-derived vesicles, mitochondrial dynamics (fusion and fission process shaping mitochondrial morphology), and mitophagy-the process in charge of the removal of mitochondria though autophagy. The loss of skeletal muscle mass (atrophy) is a major health problem worldwide, especially in older people. Currently, there is no treatment to counteract the progressive decline in skeletal muscle mass and strength that occurs with aging, a process termed sarcopenia. There is increasing data, including our own, suggesting that accumulation of dysfunctional mitochondria contributes to the development of sarcopenia. Impairments in mitochondrial dynamics and mitophagy were recently proposed to contribute to sarcopenia. This review summarizes the current state of knowledge on the role played by mitochondrial dynamics and mitophagy in skeletal muscle health and in the development of sarcopenia. We also highlight recent studies showing that enhancing mitophagy in skeletal muscle is a promising therapeutic target to prevent or even treat skeletal muscle dysfunction in the elderly.

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