Pyruvate induces mitochondrial biogenesis by a PGC-1 α-independent mechanism

Leanne Wilson, Qing Yang, Joseph D. Szustakowski, P. Scott Gullicksen, Reza Halse
2007 American Journal of Physiology - Cell Physiology  
dative cells increase mitochondrial mass in response to stimuli such as changes in energy demand or cellular differentiation. This plasticity enables the cell to adapt dynamically to achieve the necessary oxidative capacity. However, the pathways involved in triggering mitochondrial biogenesis are poorly defined. The present study examines the impact of altering energy provision on mitochondrial biogenesis in muscle cells. C2C12 myoblasts were chronically treated with supraphysiological levels
more » ... f sodium pyruvate for 72 h. Treated cells exhibited increased mitochondrial protein expression, basal respiratory rate, and maximal oxidative capacity. The increase in mitochondrial biogenesis was independent of increases in peroxisomal proliferator activator receptor-␥ coactivator-1␣ (PGC-1␣) and PGC-1␤ mRNA expression. To further assess whether PGC-1␣ expression was necessary for pyruvate action, cells were infected with adenovirus containing shRNA for PGC-1␣ before treatment with pyruvate. Despite a 70% reduction in PGC-1␣ mRNA, the effect of pyruvate was preserved. Furthermore, pyruvate induced mitochondrial biogenesis in primary myoblasts from PGC-1␣ null mice. These data suggest that regulation of mitochondrial biogenesis by pyruvate in myoblasts is independent of PGC-1␣, suggesting the existence of a novel energysensing pathway regulating oxidative capacity. oxidative metabolism; peroxisomal proliferator activator receptor-␥ coactivator-1␣, mitochondria; muscle
doi:10.1152/ajpcell.00428.2006 pmid:17182725 fatcat:ayszzgx2jjbahggxzdxz2hchay