Pyruvate induces mitochondrial biogenesis by a PGC-1alpha independent mechanism. Mus musculus

The present study examines the impact of altering energy provision on mitochondrial biogenesis in muscle cells. C2C12 myoblasts were chronically treated with supraphysiological levels of sodium pyruvate for 72 hr. Treated cells exhibited increased mitochondrial protein expression, basal respiratory rate and maximal oxidative capacity. The increase in mitochondrial biogenesis was independent of increases in PGC-1alpha and PGC-1alpha mRNA expression. To further assess whether PGC-1alpha expression was necessary for pyruvate action, cells were infected with adenovirus containing shRNA for PGC-1alpha prior to treatment with pyruvate. Despite a 70% reduction in PGC-1alpha mRNA the effect of pyruvate was preserved. Furthermore, pyruvate induced mitochondrial biogenesis in primary myoblasts from PGC-1alpha null mice. These data suggest that regulation of mitochondrial biogenesis by pyruvate in myoblasts is independent of PGC-1alpha, suggesting the existence of a novel energy-sensing pathway regulating oxidative capacity. Keywords: basal state versus treatment at one time point Overall design: C2C12 myoblasts were incubated with either basal media or basal media supplemented with 50 mM sodium pyruvate for 72 hr. Total RNA was extracted using TRIzol and GeneChip experiment was conducted using Gene Chip Mouse Genome 430 2.0 Expression Array. A Gene Chip analysis for each condition was performed in triplicate.