Abstract
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.
Highlights
We critically summarized the current state of knowledge on the role played by mitochondrial dynamics and mitophagy in skeletal muscle health and in the development of sarcopenia
Data from mechanistic studies have clearly highlighted that mitochondrial dynamics and mitophagy are critical to skeletal muscle and mitochondrial health
Whether impairment in mitochondrial dynamics contributes to sarcopenia still remains unknown, as the literature is filled with conflicting data
Summary
Skeletal muscle, which accounts for over 40% of total body mass, is highly adaptable and of critical importance for general health. It plays key roles in posture, mobility, thermogenesis, glucose homeostasis, and energy metabolism. Given the increasing population of older adults all over the world, it is not surprising that the age-related decline in muscle mass, strength, and function has become a major global health concern. Several biological mechanisms have been proposed to explain the development of sarcopenia [8] Among these mechanisms, strong experimental evidence indicates that the accumulation of mitochondrial dysfunction plays an important role in the muscle aging process. We review recent evidence showing that targeting mitophagy might be a promising strategy to prevent or even treat sarcopenia
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