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

Darren J Player ,Mark P Lewis

doi:10.7457/cmep.v1i1.e2

Darren J Player , Mark P Lewis

Open Access

https://doi.org/10.7457/cmep.v1i1.e2

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Abstract

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.

Highlights

Skeletal muscle has the intrinsic ability to adapt in response to physical activity
At the onset of contraction, disturbances in muscle cellular homeostasis induce a broad spectrum of biochemical and molecular events. These events provide immediate energy supply for sustained contraction and induce the synthesis of gene transcripts and proteins required for the adaptive response to change the phenotypic characteristics necessary to meet subsequent functional demands
The aim of this review is to discuss the acute biochemical, intracellular signalling and transcriptional responses to exercise that have been proposed to play key roles in the adaptive response known as mitochondrial biogenesis

Summary

Introduction

Skeletal muscle has the intrinsic ability to adapt in response to physical activity (exercise). At the onset of contraction, disturbances in muscle cellular homeostasis induce a broad spectrum of biochemical and molecular events. These events provide immediate energy supply for sustained contraction and induce the synthesis of gene transcripts and proteins required for the adaptive response to change the phenotypic characteristics necessary to meet subsequent functional demands. Despite the potential for physical activity in targeting these diseases, the exact cellular and molecular mechanisms that govern the adaptations have only recently begun to be understood (Coffey et al, 2006). A surge in research investigating the molecular adaptations to exercise has provided us with a broad spectrum of potential mechanisms

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