Skeletal Muscle Fibre-Specific Knockout of P53 does not Reduce Mitochondrial Content or Enzyme Activity > 자유게시판

Tumour protein p53 (p53) was initially characterised as a tumour suppressor protein (Matoba et al., 2006; Vousden and Prives, 2009; Muller and Vousden, 2013), serving to regulate cellular metabolism and proliferation (Zhou et al., 2003; Bensaad et al., 2006; Matoba et al., 2006). More recently, a functional role of p53 for in vivo skeletal muscle physiology has been proposed, following observations that p53 can regulate apoptosis (Saleem et al., 2009), atrophy (Fox et al., Alpha Surge Male official site 2014), autophagy (Saleem et al., 2014), mitochondrial DNA stability (Saleem and Hood, 2013; Safdar et al., 2016), post-exercise signalling (Saleem et al., 2009, 2014), mitochondrial function (Park et al., 2009; Saleem et al., 2009, 2014; Wang et al., 2013) and endurance performance (Park et al., 2009; Saleem et al., 2009; Wang et al., 2013) within skeletal muscle. Whole-body knockout (KO) of p53 in mice results in a deficient skeletal muscle mitochondrial phenotype (Park et al., 2009; Saleem et al., 2009), displaying reduced mitochondrial mass, mtDNA copy number, cytochrome-c oxidase enzyme activity, and state 3 respiration (Park et al., 2009; Saleem et al., 2009). As a consequence, endurance capacity and voluntary wheel running are also reduced in p53 KO mice (Park et al., 2009; Saleem et al., 2009). In comparison, oncogenic p53 mutations found in the Li-Fraumeni syndrome increase in vivo skeletal muscle oxidative phosphorylation in humans (Wang et al., 2013), while mitochondrial respiration and content of electron transport chain proteins is increased in primary myoblasts from Li-Fraumeni carriers and in mice carrying a p53 R712H polymorphism (Wang et al., 2013). Thus, it is clear that p53 plays an important role in mitochondrial metabolism and function.