Misregulation of autophagy and protein degradation systems in myopathies and muscular dystrophies

• Published in: Journal of cell science Vol. 126; no. Pt 23; pp. 5325 - 5333
• Main Authors: Sandri, Marco, Coletto, Luisa, Grumati, Paolo, Bonaldo, Paolo
• Format: Journal Article
• Language: English
• Published: England 01-12-2013
• Subjects: Autophagy - genetics; Gene Expression Regulation; Humans; Lysosomes - metabolism; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular Atrophy - genetics; Muscular Atrophy - metabolism; Muscular Atrophy - pathology; Muscular Dystrophies - genetics; Muscular Dystrophies - metabolism; Muscular Dystrophies - pathology; Proteasome Endopeptidase Complex - metabolism; Proteolysis; Signal Transduction; Ubiquitination; Ubiquitins - genetics; Ubiquitins - metabolism; Dystrophy; Muscle wasting; Autophagy; Skeletal muscle; Duchenne; Myopathy
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.114041

A number of recent studies have highlighted the importance of autophagy and the ubiquitin-proteasome in the pathogenesis of muscle wasting in different types of inherited muscle disorders. Autophagy is crucial for the removal of dysfunctional organelles and protein aggregates, whereas the ubiquitin-proteasome is important for the quality control of proteins. Post-mitotic tissues, such as skeletal muscle, are particularly susceptible to aged or dysfunctional organelles and aggregation-prone proteins. Therefore, these degradation systems need to be carefully regulated in muscles. Indeed, excessive or defective activity of the autophagy lysosome or ubiquitin-proteasome leads to detrimental effects on muscle homeostasis. A growing number of studies link abnormalities in the regulation of these two pathways to myofiber degeneration and muscle weakness. Understanding the pathogenic role of these degradative systems in each inherited muscle disorder might provide novel therapeutic targets to counteract muscle wasting. In this Commentary, we will discuss the current view on the role of autophagy lysosome and ubiquitin-proteasome in the pathogenesis of myopathies and muscular dystrophies, and how alteration of these degradative systems contribute to muscle wasting in inherited muscle disorders. We will also discuss how modulating autophagy and proteasome might represent a promising strategy for counteracting muscle loss in different diseases.