Mitochondrial activity regulates myoblast differentiation by control of c-Myc expression.
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.
Seyer
Pascal
P
UMR 866 Différenciation Cellulaire et Croissance (INRA-UMII-ENSAM), Unité d'Endocrinologie Cellulaire, Institut National de la Recherche Agronomique, Montpellier Cedex 1, France.
Grandemange
Stéphanie
S
Busson
Muriel
M
Carazo
Angel
A
Gamaléri
Frédéric
F
Pessemesse
Laurence
L
Casas
François
F
Cabello
Gérard
G
Wrutniak-Cabello
Chantal
C
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002701:Chloramphenicol / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D017570:MyoD Protein / Q000235:genetics; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018008:Myogenin / Q000235:genetics; D018995:Myosin Heavy Chains / Q000378:metabolism; D010444:Peptide Elongation Factor Tu / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011784:Quail; D011950:Receptors, Cholinergic / Q000235:genetics; D014162:Transfection
D017570:MyoD Protein; D018008:Myogenin; D016271:Proto-Oncogene Proteins c-myc; D011950:Receptors, Cholinergic; D002701:Chloramphenicol; D003576:Electron Transport Complex IV; D010444:Peptide Elongation Factor Tu; D018995:Myosin Heavy Chains