Mitochondrial activity regulates myoblast differentiation by control of c-Myc expression

✍ Scribed by Pascal Seyer; Stéphanie Grandemange; Muriel Busson; Angel Carazo; Frédéric Gamaléri; Laurence Pessemesse; François Casas; Gérard Cabello; Chantal Wrutniak-Cabello

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 700 KB
• Volume: 207
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20539

✦ Synopsis

Abstract

We have previously shown that mitochondrial activity is an important regulator of myoblast differentiation, partly through processes targeting myogenin expression. Here, we investigated the possible involvement of c‐myc in these processes. Inhibition of mitochondrial activity by chloramphenicol abrogated the decrease in c‐myc mRNA and protein levels occurring at the onset of terminal differentiation. Conversely, stimulation of mitochondrial activity by overexpression of the T3 mitochondrial receptor (p43) down‐regulated c‐myc expression. In addition, c‐myc overexpression mimicked the influence of mitochondrial activity inhibition on myoblast differentiation. Moreover, like chloramphenicol, c‐myc overexpression strongly inhibited the myogenic influence of p43 overexpression. These data suggest that c‐Myc is an important target of mitochondrial activity involved in the myogenic influence of the organelle. Lastly, we found that chloramphenicol influence is negatively related to the frequency of post‐mitotic myoblasts in the culture at the onset of treatment, and cell cycle analyses demonstrated that the frequency of myoblasts in G0–G1 phase at cell confluence is increased by p43 overexpression and decreased by chloramphenicol or c‐myc overexpression. These results suggest that irreversible myoblast withdrawal from the cell cycle is a target of mitochondrial activity by control of c‐Myc expression. J. Cell. Physiol. 207: 75–86, 2006. © 2005 Wiley‐Liss, Inc.