Mitochondrial dysfunction and skeletal muscle atrophy: Causes, mechanisms, and treatment strategies.

The role of mitochondrial dysfunction in mediating skeletal muscle atrophy and therapeutic approaches. [Display omitted] • Skeletal muscle atrophy is characterized by a decrease in muscle strength and endurance, negatively affecting the quality of life. • Mitochondria in skeletal muscle atrophy play a critical role in several processes such as ATP production, metabolic processes, redox homeostasis, and regulation of apoptosis. • Mitochondrial signaling pathways to skeletal muscle atrophy in CVDs include ubiquitin–proteasome system, autophagy, mitophagy, mitochondrial fission–fusion and mitochondrial biogenesis. • Exercise, mitochondria-targeted antioxidants, and PGC-1 via in vivo transfection are some of the current therapeutic strategies for skeletal muscle atrophy. • Mitochondrial transplantation might be one of the possible therapeutic approaches for skeletal muscle atrophy. Skeletal muscle, which accounts for approximately 40% of total body weight, is one of the most dynamic and plastic tissues in the human body and plays a vital role in movement, posture and force production. More than just a component of the locomotor system, skeletal muscle functions as an endocrine organ capable of producing and secreting hundreds of bioactive molecules. Therefore, maintaining healthy skeletal muscles is crucial for supporting overall body health. Various pathological conditions, such as prolonged immobilization, cachexia, aging, drug-induced toxicity, and cardiovascular diseases (CVDs), can disrupt the balance between muscle protein synthesis and degradation, leading to skeletal muscle atrophy. Mitochondrial dysfunction is a major contributing mechanism to skeletal muscle atrophy, as it plays crucial roles in various biological processes, including energy production, metabolic flexibility, maintenance of redox homeostasis, and regulation of apoptosis. In this review, we critically examine recent knowledge regarding the causes of muscle atrophy (disuse, cachexia, aging, etc.) and its contribution to CVDs. Additionally, we highlight the mitochondrial signaling pathways involvement to skeletal muscle atrophy, such as the ubiquitin–proteasome system, autophagy and mitophagy, mitochondrial fission–fusion, and mitochondrial biogenesis. Furthermore, we discuss current strategies, including exercise, mitochondria-targeted antioxidants, in vivo transfection of PGC-1α, and the potential use of mitochondrial transplantation as a possible therapeutic approach. [ABSTRACT FROM AUTHOR]