Recent advances in measuring and understanding the regulation of exercise-mediated protein degradation in skeletal muscle

Yusuke Nishimura, Ibrahim Musa, Lars Holm, Yu-Chiang Lai

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Skeletal muscle protein turnover plays a crucial role in controlling muscle mass and protein quality control, including sarcomeric (structural and contractile) proteins. Protein turnover is a dynamic and continual process of protein synthesis and degradation. The ubiquitin proteasome system (UPS) is a key degradative system for protein degradation and protein quality control in skeletal muscle. UPS-mediated protein quality control is known to be impaired in aging and diseases. Exercise is a well-recognized, nonpharmacological approach to promote muscle protein turnover rates. Over the past decades, we have acquired substantial knowledge of molecular mechanisms of muscle protein synthesis after exercise. However, there have been considerable gaps in the mechanisms of how muscle protein degradation is regulated at the molecular level. The main challenge to understand muscle protein degradation is due in part to the lack of solid stable isotope tracer methodology to measure muscle protein degradation rate. Understanding the mechanisms of UPS with the concomitant measurement of protein degradation rate in skeletal muscle will help identify novel therapeutic strategies to ameliorate impaired protein turnover and protein quality control in aging and diseases. Thus, the goal of this present review was to highlight how recent advances in the field may help improve our understanding of exercise-mediated protein degradation. We discuss 1) the emerging roles of protein phosphorylation and ubiquitylation modifications in regulating proteasome-mediated protein degradation after exercise and 2) methodological advances to measure in vivo myofibrillar protein degradation rate using stable isotope tracer methods.

Original languageEnglish
Pages (from-to)C276-C287
JournalAJP: Cell Physiology
Issue number2
Early online date28 Jul 2021
Publication statusPublished - 1 Aug 2021


  • Animals
  • Exercise/physiology
  • Humans
  • Muscle Proteins/metabolism
  • Muscle, Skeletal/metabolism
  • Proteasome Endopeptidase Complex/metabolism
  • Protein Biosynthesis/physiology
  • Signal Transduction/physiology


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