| First Author | Uguccioni G | Year | 2011 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 300 |
| Issue | 2 | Pages | E361-71 |
| PubMed ID | 21081705 | Mgi Jnum | J:172323 |
| Mgi Id | MGI:5006915 | Doi | 10.1152/ajpendo.00292.2010 |
| Citation | Uguccioni G, et al. (2011) The importance of PGC-1alpha in contractile activity-induced mitochondrial adaptations. Am J Physiol Endocrinol Metab 300(2):E361-71 |
| abstractText | The transcriptional coactivator PPARgamma coactivator-1alpha (PGC-1alpha) is a critical regulator of mitochondrial content and function in skeletal muscle. PGC-1alpha may also mediate mitochondrial adaptations in response to chronic contractile activity (CCA). To characterize the essential role of PGC-1alpha in organelle biogenesis, CC murine myotubes were transfected with PGC-1alpha-specific siRNA and subjected to electrical stimulation-evoked CCA. CCA enhanced cytochrome c oxidase (COX) activity along with increases in several nuclear-encoded mitochondrial proteins. Transfection of PGC-1alpha siRNA decreased protein and mRNA of the coactivator by 60%, resulting in decrements of Tfam and COX-IV proteins. The mRNA expression of the PGC-1 family members PGC-1beta and PRC, as well as transcription factors NRF-1/2 and ERRalpha, did not exhibit compensatory changes in response to PGC-1alpha depletion. However, phosphorylation of AMPK was enhanced in myotubes with reduced levels of PGC-1alpha. This suggests the presence of metabolic compensatory stress signals in cells deficient in PGC-1alpha. Our findings reveal that the CCA-induced increases in COX-IV protein and overall mitochondrial content, using both COX activity and organelle fluorescence, are dependent on PGC-1alpha. However, this was not the case for all proteins, since decreased levels of the coactivator did not attenuate the increases in Tfam and cytochrome c in response to CCA. These data indicate that PGC-1alpha is necessary for most of the mitochondrial adaptations that occur with CCA but that there are additional pathways that function in parallel with PGC-1alpha to mediate the elevated expression of specific nuclear-encoded proteins that are vital for mitochondrial function and cell viability. |
