The effects of contractile activity on mitochondrial adaptations in PGC‐1alpha‐deficient muscle cells

Abstract

PGC‐1α is a well established mediator of mitochondrial content and function in skeletal muscle. However, the essentiality of the coactivator for mitochondrial biogenesis (MB) in response to chronic contractile activity (CCA) is still in question. Thus, we depleted skeletal muscle C2C12 cells of PGC‐1α using siRNA, then stimulated the myotubes to induced MB. A 60% reduction in PGC‐1α using siRNA resulted in a compensatory increase in AMPK phosphorylation, but had no effect on the mRNA expression of PGC‐1β, PRC, NRF‐1/2 or YY1, proteins that may have served to compensate for low PGC‐1α levels. In response to CCA, we found that a normal induction of PGC‐1α in response to CCA was required to observe the typical changes in MB, as revealed by attenuated increases in COX activity (p<0.05) and mitochondrial immunofluorescence. Decreased levels of PGC‐1α also reduced the CCA‐evoked increases in COXIV. However, PGC‐1α was not necessary for the CCA‐induced changes of all mitochondrial proteins since Tfam and cytochrome c displayed normal increases, regardless of attenuated PGC‐1α levels. Thus, PGC‐1α is necessary for the normal induction of mitochondrial biogenesis, and the coactivator likely functions with parallel pathways to mediate increases in mitochondrial proteins with CCA.