The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass
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Cellular and Molecular Life Sciences
REVIEW
The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass Vanina Romanello1,2 · Marco Sandri1,2,3 Received: 26 June 2020 / Revised: 2 September 2020 / Accepted: 28 September 2020 © The Author(s) 2020
Abstract The dynamic coordination of processes controlling the quality of the mitochondrial network is crucial to maintain the function of mitochondria in skeletal muscle. Changes of mitochondrial proteolytic system, dynamics (fusion/fission), and mitophagy induce pathways that affect muscle mass and performance. When muscle mass is lost, the risk of disease onset and premature death is dramatically increased. For instance, poor quality of muscles correlates with the onset progression of several age-related disorders such as diabetes, obesity, cancer, and aging sarcopenia. To date, there are no drug therapies to reverse muscle loss, and exercise remains the best approach to improve mitochondrial health and to slow atrophy in several diseases. This review will describe the principal mechanisms that control mitochondrial quality and the pathways that link mitochondrial dysfunction to muscle mass regulation. Keywords Atrophy · Mitochondria · Fission · Fusion · Mitochondrial proteostasis · Autophagy · Mitophagy · Skeletal muscle · FGF21 · Myokines
Introduction Mitochondrial dysfunction has been linked to muscle function loss that occurs in several age-related metabolic disorders such as diabetes, obesity, cancer, and aging sarcopenia. In these conditions, the decrease in muscle mass is a significant health problem that worsens life quality and increases morbidity and mortality. Instead, maintaining a healthy skeletal muscle mass is associated with a lower risk of mortality [1, 2], highlighting a correlation between muscle health and whole-body homeostasis. Skeletal muscle, the most abundant tissue in the human body, is a major site of metabolic activity that regulates carbohydrates, lipids, and protein homeostasis. Energy requirements during intense * Vanina Romanello [email protected] * Marco Sandri [email protected] 1
Venetian Institute of Molecular Medicine, via Orus 2, 35129 Padova, Italy
2
Department of Biomedical Science, University of Padova, via G. Colombo 3, 35100 Padova, Italy
3
Department of Medicine, McGill University, Montreal, Canada
contraction in skeletal muscles increase to 100-fold the consumption of ATP [3]. To sustain this high energy demand, cardiac and skeletal muscles rely on oxidative phosphorylation (OXPHOS) for ATP production. Therefore, maintaining a functional mitochondrial network in this tissue is fundamental to sustain the metabolic demands imposed by contraction, ultimately regulating fuel utilization, energy expenditure, and general metabolism.
Signaling pathways regulating muscle mass The muscle mass in adulthood is defined by the dynamic balance between protein synthesis and protein degradation. Mechanical overload or anabolic hormonal stimulation shifts the ba
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