Mechanisms of skeletal muscle atrophy.
OBJECTIVE
Recent clinical and mechanistic studies have shown that increased proteolysis is a major determinant of muscle wasting in numerous catabolic states and of alterations in myopathies or dystrophies. The implications of these observations for improving muscle mass and function are discussed.


RESULTS
Several proteolytic systems (i.e. the ubiquitin-proteasome system, the lysosomal, the Ca-dependent, and the caspase systems) are responsible for muscle wasting. The Ca-dependent and caspase systems may initiate myofibrillar proteolysis. The ubiquitin-proteasome system is believed to degrade actin and myosin heavy chain and, consequently, plays a major role in muscle wasting. Multiple steps in the ubiquitin-proteasome system (ubiquitination, deubiquitination, proteasome activities) are upregulated in muscle wasting diseases. Few key components of the ubiquitin-proteasome system that are strictly necessary for muscle wasting have been so far characterized. Recent studies have led to the elucidation of various signaling pathways of the ubiquitin-proteasome system that are activated in muscle wasting conditions.


CONCLUSIONS
Although the precise role of the different muscle proteolytic machineries is still largely unknown, current studies are leading to new pharmacologic approaches that can be useful in blocking or partially preventing muscle wasting or improving muscle function in human patients.
Ventadour
Sophie
S
National Institute for Agricultural Research and Human Nutrition Research Centre of Clermont-Ferrand, Human Nutrition Unit, UMR 1019, Ceyrat, France.
Attaix
Didier
D
D002100:Cachexia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism; D018908:Muscle Weakness / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex; D020543:Proteome; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
D009124:Muscle Proteins; D020543:Proteome; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex