Myoblasts rely on TAp63 to control basal mitochondria respiration

p53, with its family members p63 and p73, have been shown to promote myoblast differentiation by regulation of the function of the retinoblastoma protein and by direct activation of p21(Cip)(/)(Waf1) and p57(Kip2), promoting cell cycle exit. In previous studies, we have demonstrated that the TAp63 gamma isoform is the only member of the p53 family that accumulates during in vitro myoblasts differentiation, and that its silencing led to delay in myotube fusion. To better dissect the role of TAp63 gamma in myoblast physiology, we have generated both sh-p63 and Tet-On inducible TAp63 gamma clones. Gene array analysis of sh-p63 C2C7 clones showed a significant modulation of genes involved in proliferation and cellular metabolism. Indeed, we found that sh-p63 C2C7 myoblasts present a higher proliferation rate and that, conversely, TAp63 gamma ectopic expression decreases myoblasts proliferation, indicating that TAp63 gamma specifically contributes to myoblasts proliferation, independently of p53 and p73. In addition, sh-p63 cells have a defect in mitochondria respiration highlighted by a reduction in spare respiratory capacity and a decrease in complex I, IV protein levels. These results demonstrated that, beside contributing to cell cycle exit, TAp63 gamma participates to myoblasts metabolism control.