https://www.selleckchem.com/products/bi-2493.html stantial institutional variation. Our study elucidates common clinical scenarios deemed rarely appropriate and clarifies the potential targets of quality improvement. Registration URL https//www.umin.ac.jp/ctr/index.htm. Unique identifier UMIN000020423.SIGNIFICANCE Regular contractile activity plays a critical role in maintaining skeletal muscle morphological integrity and physiological function. If the muscle is forced to stop contraction, such as during limb immobilization (IM), the IGF/Akt/mTOR signaling pathway that normally stimulates protein synthesis and inhibits proteolysis will be suppressed, whereas the FoxO-controlled catabolic pathways such as ubiquitin-proteolysis and autophagy/mitophagy will be activated and dominate, resulting in muscle fiber atrophy. Recent Advances. Mitochondria occupy a central position in regulating both protein synthesis and degradation via several redox-sensitive pathways including PGC-1α, mitochondrial fusion/fission proteins, mitophagy, and sirtuins. Prolonged IM downregulates PGC-1α due to AMPK and FoxO activation thus decreasing mitochondrial biogenesis and causing oxidative damage. Decline of mitochondrial inner membrane potential and increased mitochondrial fission can trigger cascades of mitophagy leading to loss of mitochondrial homeostasis (mitostasis), inflammation, and apoptosis. The phenotypic outcomes of these disorders are compromised muscle function and fiber atrophy. CRITICAL ISSUES Given the molecular mechanism of the pathogenesis, it is imperative that the integrity of intracellular signaling be restored to prevent the deterioration. So far, overexpression of PGC-1α via transgene and in vivo DNA transfection has been found to be effective in ameliorating mitostasis and reduces IM-induced muscle atrophy. Nutritional supplementation of select amino acids and phytochemicals also provides mechanistic and practical insights into the prevention of muscle disuse atroph