Skeletal Muscle Fibre-Specific Knockout of p53 Does Not Reduce Mitochondrial Content or Enzyme Activity

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

External organisations

  • School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. Electronic address: Axh547@bham.ac.uk.
  • Department of Human Physiology, University of Oregon, Eugene, OR, United States.

Abstract

Tumour protein 53 (p53) has been implicated in the regulation of mitochondrial biogenesis in skeletal muscle, with whole-body p53 knockout mice displaying impairments in basal mitochondrial content, respiratory capacity, and enzyme activity. This study aimed to determine the effect of skeletal muscle-specific loss of p53 on mitochondrial content and enzyme activity. Mitochondrial protein content, enzyme activity and mRNA profiles were assessed in skeletal muscle of 8-week-old male muscle fibre-specific p53 knockout mice (p53 mKO) and floxed littermate controls (WT) under basal conditions. p53 mKO and WT mice displayed similar content of electron transport chain proteins I-V and citrate synthase enzyme activity in skeletal muscle. In addition, the content of proteins regulating mitochondrial morphology (MFN2, mitofillin, OPA1, DRP1, FIS1), fatty acid metabolism (β-HAD, ACADM, ACADL, ACADVL), carbohydrate metabolism (HKII, PDH), energy sensing (AMPKα2, AMPKβ2), and gene transcription (NRF1, PGC-1α, and TFAM) were comparable in p53 mKO and WT mice (p > 0.05). Furthermore, p53 mKO mice exhibited normal mRNA profiles of targeted mitochondrial, metabolic and transcriptional proteins (p > 0.05). Thus, it appears that p53 expression in skeletal muscle fibres is not required to develop or maintain mitochondrial protein content or enzyme function in skeletal muscle under basal conditions.

Details

Original languageEnglish
Article number941
JournalFrontiers in Physiology
Volume8
Publication statusPublished - 4 Dec 2017

Keywords

  • p53, skeletal muscle, mitochondria, metabolism, PGC-1α