PGC1α and mitochondrial metabolism – emerging concepts and relevance in ageing and neurodegenerative disorders

Abstract

Summary PGC1α is a transcriptional coactivator that is a central inducer of mitochondrial biogenesis in cells. Recent work highlighted that PGC1α can also modulate the composition and functions of individual mitochondria. Therefore, it is emerging that PGC1α is controlling global oxidative metabolism by performing two types of remodelling: (1) cellular remodelling through mitochondrial biogenesis, and (2) organelle remodelling through alteration in the intrinsic properties of mitochondria. The elevated oxidative metabolism associated with increased PGC1α activity could be accompanied by an increase in reactive oxygen species (ROS) that are primarily generated by mitochondria. However, increasing evidence suggests that this is not the case, as PGC1α is also a powerful regulator of ROS removal by increasing the expression of numerous ROS-detoxifying enzymes. Therefore, PGC1α, by controlling both the induction of mitochondrial metabolism and the removal of its ROS by-products, would elevate oxidative metabolism and minimize the impact of ROS on cell physiology. In this Commentary, we discuss how the biogenesis and remodelling of mitochondria that are elicited by PGC1α contribute to an increase in oxidative metabolism and the preservation of ROS homeostasis. Finally, we examine the importance of these findings in ageing and neurodegenerative disorders, conditions that are associated with impaired mitochondrial functions and ROS balance.