Mitochondrial Activity Is Involved in the Regulation of Myoblast Differentiation through Myogenin Expression and Activity of Myogenic Factors

• Published in: The Journal of biological chemistry 2000-01, Vol.275 (4), p.2733-2744
• Main Authors: Rochard, Pierrick, Rodier, Anne, Casas, François, Cassar-Malek, Isabelle, Marchal-Victorion, Sophie, Daury, Laetitia, Wrutniak, Chantal, Cabello, Gérard
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Neoplasm - genetics; Aves; Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone; Cell Differentiation - physiology; Cell Division - physiology; Cell Line; Cell Nucleus - metabolism; chloramphenicol; Chloramphenicol - pharmacology; CMD1 gene; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - physiology; Mitochondrial Proteins; myf5 gene; MyoD gene; myogenesis; myogenin; Myogenin - genetics; oligomycin; p43 protein; Peptide Elongation Factor Tu - genetics; Quail
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.275.4.2733

To characterize the regulatory pathways involved in the inhibition of cell differentiation induced by the impairment of mitochondrial activity, we investigated the relationships occurring between organelle activity and myogenesis using an avian myoblast cell line (QM7). The inhibition of mitochondrial translation by chloramphenicol led to a potent block of myoblast differentiation. Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone and oligomycin, which affect the organelle at different levels, exerted a similar influence. In addition, we provided evidence that this phenomenon was not the result 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 activity in an actual regulation of myogenesis is further supported by results demonstrating that the muscle regulatory gene myogenin, in contrast toCMD1 (chicken MyoD) and myf5, is a specific transcriptional target of mitochondrial activity. Whereas myogenin mRNA and protein levels were down-regulated by chloramphenicol treatment, they were up-regulated by p43 overexpression, in a positive relationship with the expression level of the transgene. We also found that myogenin or CMD1 overexpression in chloramphenicol-treated myoblasts did not restore differentiation, thus indicating that an alteration in mitochondrial activity interferes with the ability of myogenic factors to induce terminal differentiation.