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

Int J Biochem Cell Biol. 2013 Oct;45(10):2121-9. doi: 10.1016/j.biocel.2013.04.023. Epub 2013 May 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Humans
  • Lysosomes / metabolism*
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology*
  • Proteasome Endopeptidase Complex / metabolism*
  • Signal Transduction
  • Ubiquitin / metabolism*

Substances

  • Muscle Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex