Mechanisms activating PGC-1α and consequential transcriptional mechanisms following exercise: A mini review

Darren J Player, Mark P Lewis


Skeletal muscle has the ability to adapt in response to exercise to increase the oxidative potential of the tissue. The adaptive response contributes to a favourable phenotype, increasing the ability of the tissue to augment superior fat oxidation and glucose uptake. In this respect, exercise, particularly endurance modes of exercise, forms a strong preventative and treatment strategy for metabolic diseases. The acute disturbance of homeostasis in response to muscle contraction during exercise stimulates a variety of intra-cellular mechanisms that signal to a putative stimulator of mitochondrial biogenesis, PGC-1α. The activation of these mechanisms is explored in this mini-review, drawing upon in vivo, ex vivo and in vitro data. Additionally, the effect of PGC-1α activation and the consequential transcriptional regulatory network is discussed in relation to stimulating mitochondrial biogenesis. Our understanding of these mechanisms has been hindered by the complex nature of the coordination of both nuclear and mitochondrial genomes. Further, the nature of in vivo experimentation with respect to exercise modalities and nutritional manipulation has often presented conflicting findings. Delineating the mechanisms further with highly controlled in vivo experiments, along with targeted in vitro experiments will define targets for potential genetic and pharmacological therapies in the future.


Exercise; PGC-1α; mitochondria; skeletal muscle


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Cell Mol Exerc Physiol (CMEP) Online ISSN: 2049-419X Prefix DOI: 10.7457