Protein breakdown in muscle wasting: role of autophagy-lysosome and ubiquitin-proteasome - PubMed (original) (raw)

Review

Protein breakdown in muscle wasting: role of autophagy-lysosome and ubiquitin-proteasome

Marco Sandri. Int J Biochem Cell Biol. 2013 Oct.

Abstract

Skeletal muscle adapts its mass as consequence of physical activity, metabolism and hormones. Catabolic conditions or inactivity induce signaling pathways that regulate the process of muscle loss. Muscle atrophy in adult tissue occurs when protein degradation rates exceed protein synthesis. Two major protein degradation pathways, the ubiquitin-proteasome and the autophagy-lysosome systems, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These degradation systems are controlled by a transcription dependent program that modulates the expression of rate-limiting enzymes of these proteolytic systems. The transcription factors FoxO, which are negatively regulated by Insulin-Akt pathway, and NF-κB, which is activated by inflammatory cytokines, were the first to be identified as critical for the atrophy process. In the last years a variety of pathways and transcription factors have been found to be involved in regulation of atrophy. This review will focus on the last progress in ubiquitin-proteasome and autophagy-lysosome systems and their involvement in muscle atrophy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

Keywords: Atrophy; Autophagy; FoxO; Muscle wasting; Skeletal muscle; Ubiquitin protesaome.

Copyright © 2013 The Author. Published by Elsevier Ltd.. All rights reserved.

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Figures

Fig. 1

Fig. 1

Signaling modules responsible for autophagy-lysosome pathway in the adult. The different modules are: autophagosome formation, selective autophagic removal of mitochondria, autophagosome docking and fusion with lysosome and new lysosome formation. Each module is controlled by different pathways and factors. The dotted lines point to mechanisms that are not yet known.

Fig. 2

Fig. 2

Signaling modules that are important therapeutic targets to counteract muscle wasting. Most of the pathways converge onto a final common pathway centered on Akt-mTOR-FoxO module. The dotted lines point to pathways that are not yet dissected.

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