Regulation of mitochondrial biogenesis during myogenesis.
Pathways involved in mitochondrial biogenesis associated with myogenic differentiation are poorly defined. Therefore, C(2)C(12) myoblasts were differentiated into multi-nucleated myotubes and parameters/regulators of mitochondrial biogenesis were investigated. Mitochondrial respiration, citrate synthase- and beta-hydroxyacyl-CoA dehydrogenase activity as well as protein content of complexes I, II, III and V of the mitochondrial respiratory chain increased 4-8-fold during differentiation. Additionally, an increase in the ratio of myosin heavy chain (MyHC) slow vs MyHC fast protein content was observed. PPAR transcriptional activity and transcript levels of PPAR-alpha, the PPAR co-activator PGC-1alpha, mitochondrial transcription factor A and nuclear respiratory factor 1 increased during differentiation while expression levels of PPAR-gamma decreased. In conclusion, expression and activity levels of genes known for their regulatory role in skeletal muscle oxidative capabilities parallel the increase in oxidative parameters during the myogenic program. In particular, PGC-1alpha and PPAR-alpha may be involved in the regulation of mitochondrial biogenesis during myogenesis.
Department of Respiratory Medicine, Maastricht University Medical Centre+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. a.remels@pul.unimaas.nl
A H V
AH
Remels
R C J
RC
Langen
P
P
Schrauwen
G
G
Schaart
A M W J
AM
Schols
H R
HR
Gosker
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019069:Cell Respiration / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics; D051379:Mice; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology; D032446:Myoblasts / Q000166:cytology / Q000502:physiology; D010085:Oxidative Phosphorylation; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D004272:DNA, Mitochondrial; D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms