About this Research Topic
Atrophy of skeletal muscle is an inevitable sequela of lack of use (e.g., bed-ridden patients, spinal cord injuries), fasting or many diseases (e.g., cancer cachexia, diabetes, renal failure, cardiac failure, sepsis and neuromuscular diseases (ALS)). The major loss of mass during atrophy results largely from the accelerated destruction of the muscle’s contractile unit, the myofibrils, which comprise more than 60% of muscle proteins and are responsible for force production. Their loss during atrophy leads to reduced contractile force, fatigue and weakness, and in many human diseases to reduced quality of life, and increased morbidity and mortality. The mechanism for myofibril turnover has long been uncertain, although the ubiquitin-proteasome system seems to play a major role. Recent studies demonstrate that myofibril breakdown during atrophy is an ordered process involving the ubiquitin ligases, MuRF1 and Trim32. MuRF1 is essential for the ubiquitin-dependent degradation of proteins comprising the thick filament, while Trim32 catalyzes the disassembly and degradation of the desmin cytoskeleton, Z-band, and thin filament proteins, which are linked processes. Additional studies suggest a role for caspases and calpains in the disassembly of this rigid and complex structure.
The goal of this topic is to bring together all the key experiments, recent advances and new findings in order to increase our understanding of the molecular mechanisms mediating disassembly of myofibrils. This may facilitate the identification of key players in this process as potential drug targets for treatment of loss of myofibril and muscle mass during atrophy.
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