Mitochondrial activity is involved in the regulation of myoblast differentiation through myogenin expression and activity of myogenic factors

To characterize the regulatory pathways involved in the inhibition of cell differentiation induced by the impairment of mitochondrial activity, me inv estigated the relationships occurring between organelle activity and myogen esis using an avian myoblast cell line (QM7). The inhibition of mitochondri al translation by chloramphenicol led to a potent block of myoblast differe ntiation, Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone and oligomy cin, which affect the organelle at different levels, exerted a similar infl uence. In addition, we provided evidence that this phenomenon was not the r esult of an alteration in cell viability. Conversely, overexpression of the mitochondrial T3 receptor (p43) stimulated organelle activity and strongly potentiated myoblast differentiation. The involvement of mitochondrial act ivity in an actual regulation of myogenesis is further supported by results demonstrating that the muscle regulatory gene myogenin, in contrast to CMD 1 (chicken MyoD) and myf5, is a specific transcriptional target of mitochon drial activity. Whereas myogenin mRNA and protein levels were down-regulate d by chloramphenicol treatment, they were up-regulated by p43 overexpressio n, in a positive relationship with the expression level of the transgene, W e also found that myogenin or CMD1 overexpression in chloramphenicol-treate d myoblasts did not restore differentiation, thus indicating that an altera tion in mitochondrial activity interferes with the ability of myogenic fact ors to induce terminal differentiation.