title: P43-dependent mitochondrial activity regulates myoblast differentiation and slow myosin isoform expression by control of Calcineurin expression.
abstract: We have previously shown that mitochondrial protein synthesis regulates myoblast differentiation, partly through the control of c-Myc expression, a cellular oncogene regulating myogenin expression and myoblast withdrawal from the cell cycle. In this study we provide evidence of the involvement of Calcineurin in this regulation. In C2C12 myoblasts, inhibition of mitochondrial protein synthesis by chloramphenicol decreases Calcineurin expression. Conversely, stimulation of this process by overexpressing the T3 mitochondrial receptor (p43) increases Calcineurin expression. Moreover, expression of a constitutively active Calcineurin (ΔCN) stimulates myoblast differentiation, whereas a Calcineurin antisense has the opposite effect. Lastly, ΔCN expression or stimulation of mitochondrial protein synthesis specifically increases slow myosin heavy chain expression. In conclusion, these data clearly suggest that, partly via Calcineurin expression, mitochondrial protein synthesis is involved in muscle development through the control of myoblast differentiation and probably the acquisition of the contractile and metabolic phenotype of muscle fibres.
authors.affiliation: UMR 866 Différenciation Cellulaire et Croissance (INRA-UMI-UMII), Unité d'Endocrinologie Cellulaire, Institut National de la Recherche Agronomique (INRA), 2 Place Viala, 34060 Montpellier Cedex 1, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Seyer
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Grandemange
authors.forename: Pierrick
authors.initials: P
authors.lastname: Rochard
authors.forename: Muriel
authors.initials: M
authors.lastname: Busson
authors.forename: Laurence
authors.initials: L
authors.lastname: Pessemesse
authors.forename: François
authors.initials: F
authors.lastname: Casas
authors.forename: Gérard
authors.initials: G
authors.lastname: Cabello
authors.forename: Chantal
authors.initials: C
authors.lastname: Wrutniak-Cabello
mesh_terms: D000818:Animals; D001717:Birds; D019703:Calcineurin / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008931:Mitochondria, Muscle / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D009218:Myosins / Q000096:biosynthesis* / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C514492:Aimp1 protein, mouse; D016207:Cytokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D019703:Calcineurin; D009218:Myosins