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The importance of PGC-1α in contractile activity-induced mitochondrial adaptations.
Am J Physiol Endocrinol Metab. 2011 Feb; 300(2):E361-71.AJ

Abstract

The transcriptional coactivator PPARγ coactivator-1α (PGC-1α) is a critical regulator of mitochondrial content and function in skeletal muscle. PGC-1α may also mediate mitochondrial adaptations in response to chronic contractile activity (CCA). To characterize the essential role of PGC-1α in organelle biogenesis, C₂C₁₂ murine myotubes were transfected with PGC-1α-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-1α 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-1β and PRC, as well as transcription factors NRF-1/2 and ERRα, did not exhibit compensatory changes in response to PGC-1α depletion. However, phosphorylation of AMPK was enhanced in myotubes with reduced levels of PGC-1α. This suggests the presence of metabolic compensatory stress signals in cells deficient in PGC-1α. 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-1α. 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-1α is necessary for most of the mitochondrial adaptations that occur with CCA but that there are additional pathways that function in parallel with PGC-1α to mediate the elevated expression of specific nuclear-encoded proteins that are vital for mitochondrial function and cell viability.

Authors+Show Affiliations

York University, Toronto, ON, Canada.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21081705

Citation

Uguccioni, Giulia, and David A. Hood. "The Importance of PGC-1α in Contractile Activity-induced Mitochondrial Adaptations." American Journal of Physiology. Endocrinology and Metabolism, vol. 300, no. 2, 2011, pp. E361-71.
Uguccioni G, Hood DA. The importance of PGC-1α in contractile activity-induced mitochondrial adaptations. Am J Physiol Endocrinol Metab. 2011;300(2):E361-71.
Uguccioni, G., & Hood, D. A. (2011). The importance of PGC-1α in contractile activity-induced mitochondrial adaptations. American Journal of Physiology. Endocrinology and Metabolism, 300(2), E361-71. https://doi.org/10.1152/ajpendo.00292.2010
Uguccioni G, Hood DA. The Importance of PGC-1α in Contractile Activity-induced Mitochondrial Adaptations. Am J Physiol Endocrinol Metab. 2011;300(2):E361-71. PubMed PMID: 21081705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The importance of PGC-1α in contractile activity-induced mitochondrial adaptations. AU - Uguccioni,Giulia, AU - Hood,David A, Y1 - 2010/11/16/ PY - 2010/11/18/entrez PY - 2010/11/18/pubmed PY - 2011/3/4/medline SP - E361 EP - 71 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 300 IS - 2 N2 - The transcriptional coactivator PPARγ coactivator-1α (PGC-1α) is a critical regulator of mitochondrial content and function in skeletal muscle. PGC-1α may also mediate mitochondrial adaptations in response to chronic contractile activity (CCA). To characterize the essential role of PGC-1α in organelle biogenesis, C₂C₁₂ murine myotubes were transfected with PGC-1α-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-1α 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-1β and PRC, as well as transcription factors NRF-1/2 and ERRα, did not exhibit compensatory changes in response to PGC-1α depletion. However, phosphorylation of AMPK was enhanced in myotubes with reduced levels of PGC-1α. This suggests the presence of metabolic compensatory stress signals in cells deficient in PGC-1α. 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-1α. 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-1α is necessary for most of the mitochondrial adaptations that occur with CCA but that there are additional pathways that function in parallel with PGC-1α to mediate the elevated expression of specific nuclear-encoded proteins that are vital for mitochondrial function and cell viability. SN - 1522-1555 UR - https://www.unboundmedicine.com/medline/citation/21081705/The_importance_of_PGC_1α_in_contractile_activity_induced_mitochondrial_adaptations_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00292.2010?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -