Atrogin-1, MuRF-1, and sarcopenia

Endocrine. 2013 Feb;43(1):12-21. doi: 10.1007/s12020-012-9751-7. Epub 2012 Jul 20.


Sarcopenia is one of the leading causes of disability in the elderly. Despite the growing prevalence of sarcopenia, the molecular mechanisms that control aging-related changes in muscle mass are not fully understood. The ubiquitin proteasome system is one of the major pathways that regulate muscle protein degradation, and this system plays a central role in controlling muscle size. Atrogin-1 and MuRF-1 are two E3 ubiquitin ligases that are important regulators of ubiquitin-mediated protein degradation in skeletal muscle. In this review, we will discuss: (i) aging-related changes to skeletal muscle structure and function; (ii) the regulation of protein synthesis and protein degradation by IGF-1, TGF-β, and myostatin, with emphasis on the control of atrogin-1 and MuRF-1 expression; and (iii) the potential for modulating atrogin-1 and MuRF-1 expression to treat or prevent sarcopenia.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Enzyme Induction / drug effects
  • Humans
  • Molecular Targeted Therapy
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Protein Stability / drug effects
  • SKP Cullin F-Box Protein Ligases / biosynthesis
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Sarcopenia / drug therapy
  • Sarcopenia / metabolism*
  • Sarcopenia / pathology
  • Sarcopenia / physiopathology
  • Signal Transduction / drug effects
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / biosynthesis
  • Ubiquitin-Protein Ligases / metabolism*


  • Muscle Proteins
  • Tripartite Motif Proteins
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases
  • TRIM63 protein, human
  • Ubiquitin-Protein Ligases