The biology of PGC-1α and its therapeutic potential

In eukaryotes, cellular and. systemic metabolism is primarily controlled by mitochondrial activity. The peroxisome proliferator-activated receptor gamma coactivator let (PGC-1 alpha) is an important regulator of mitochondrial biogenesis and function. Furthermore, PGC-1 alpha controls many of the phenotypic adaptations of oxidative tissues to external and internal perturbations. By contrast, dysregulated metabolic plasticity is involved in the etiology of numerous diseases. Accordingly, modulation of PGC-1 alpha levels and activity has recently been proposed as a therapeutic option for several pathologies. However, pharmacological interventions aimed at PGC-1 alpha have to overcome inherent limitations of targeting a coactivator protein. Here, I focus on the recent breakthroughs in the identification of physiological and pathophysiological contexts involving PGC-1 alpha. In addition, perspectives regarding the therapeutic importance of PGC-1 alpha-controlled cellular and systemic metabolism are outlined.