Mitochondrial-dependent regulation of myoblast proliferation

• Published in: Experimental cell research Vol. 299; no. 1; pp. 27 - 35
• Main Authors: Duguez, Stéphanie, Sabido, Odile, Freyssenet, Damien
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.09.2004
• Subjects: Animals; Antioxidants - pharmacology; Cell cyle; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Division - drug effects; Cell Division - genetics; Cell Line; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - drug effects; Cyclins - metabolism; Down-Regulation - drug effects; Down-Regulation - genetics; Energy Metabolism - drug effects; Energy Metabolism - genetics; Flow cytometry; G1 Phase - drug effects; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Hypertrophy - chemically induced; Hypertrophy - metabolism; Mitochondria - drug effects; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - growth & development; Muscle, Skeletal - metabolism; Myoblasts - drug effects; Myoblasts - metabolism; Myoblasts - ultrastructure; Myogenesis; Oxidants - pharmacology; Proliferating Cell Nuclear Antigen - drug effects; Proliferating Cell Nuclear Antigen - metabolism; Pyruvic Acid - metabolism; Pyruvic Acid - pharmacology; Rats; Reactive Oxygen Species - metabolism; Regeneration; Regeneration - drug effects; Regeneration - genetics; Skeletal muscle; Cell cyle; Flow cytometry; Mitochondrial metabolism; Regeneration; Myogenesis; Skeletal muscle
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2004.05.017

The aim of the present study was to determine whether mitochondrial activity could regulate myoblast proliferation. We demonstrate that an increase in mitochondrial activity of L6E9 myoblasts can be easily obtained by simply raising extracellular pyruvate concentration in the culture dish. Under this condition, L6E9 myoblasts underwent a rapid growth arrest in G1 + S phases concomitant to a marked cellular hypertrophy. No sign of myoblast fusion was evident. This was accompanied by the down-regulation of proliferating cell nuclear antigen expression and an increase in p21 expression. Mitochondrial biogenesis was also stimulated, as indicated by a twofold increase in mitochondrial content. These cells exhibited a large increase in the production of reactive oxygen species that could contribute to the observed phenotypic alterations. However, exposure of pyruvate-treated cells to antioxidants did not reverse growth arrest. Similarly, exposure of control cells to oxidants did not induce growth arrest. Our observations suggest that mitochondrial activity appears to play a central role in regulating myoblast proliferation. They also argue strongly in favor of a retrograde communication establishing a mitochondrial control of nuclear gene expression that could be modulated by mitochondrial activity.