Abstract
Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.
Highlights
Muscles are the largest protein reservoir in the body
These myopathies are characterized by mutation of genes encoding proteins involved in lysosomal function, and include Pompe disease, Danon disease and X-linked myopathy with excessive autophagy (XMEA; which is associated with mutations of the VMA21 gene) (Malicdan et al, 2008; Ramachandran et al, 2009)
We have shown that physical exercise is very effective in stimulating autophagy in skeletal muscles, and that the accompanying clearance of damaged cell components and dysfunctional mitochondria is crucial for muscle homeostasis (Grumati et al, 2011b)
Summary
Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. Proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. We review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases
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