Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation

Research output: Contribution to journalArticlepeer-review

Authors

  • Vitor F. Martins
  • Kristoffer Svensson
  • Samuel A. Labarge
  • Noah C. Schlenk
  • Mary C. Esparza
  • Elisa H. Buckner
  • Gretchen A. Meyer
  • D. Lee. Hamilton
  • Simon Schenk

Colleges, School and Institutes

External organisations

  • Department of Orthopaedic Surgery, University of California, Los Angeles.
  • Biomedical Sciences Graduate Program, University of California
  • Program in Physical Therapy, Washington University School of Medicine
  • School of Sport, University of Stirling, Scotland, UK.

Abstract

Objective: Lysine acetylation is an important post-translational modification that regulates metabolic function in skeletal muscle. The acetyltransferase, general control of amino acid synthesis 5 (GCN5), has been proposed as a regulator of mitochondrial biogenesis via its inhibitory action on peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). However, the specific contribution of GCN5 to skeletal muscle metabolism and mitochondrial adaptations to endurance exercise in vivo remain to be defined. We aimed to determine whether loss of GCN5 in skeletal muscle enhances mitochondrial density and function, and the adaptive response to endurance exercise training.

Methods: We used Cre-LoxP methodology to generate mice with muscle-specific knockout of GCN5 (mKO) and floxed, wildtype (WT) littermates. We measured whole-body energy expenditure, as well as markers of mitochondrial density, biogenesis, and function in skeletal muscle from sedentary mice, and mice that performed 20 days of voluntary endurance exercise training.

Results: Despite successful knockdown of GCN5 activity in skeletal muscle of mKO mice, whole-body energy expenditure as well as skeletal muscle mitochondrial abundance and maximal respiratory capacity were comparable between mKO and WT mice. Further, there were no genotype differences in endurance exercise-mediated mitochondrial biogenesis or increases in PGC-1α protein content.

Conclusion: These results demonstrate that loss of GCN5 in vivo does not promote metabolic remodeling in mouse skeletal muscle.

Details

Original languageEnglish
Pages (from-to)1574-1584
JournalMolecular metabolism
Volume6
Issue number12
Early online date16 Oct 2017
Publication statusPublished - 1 Dec 2017

Keywords

  • acetylation , GCN5 , mitochondria , SIRT1 , deacetylase , PGC-1α