Bioenergetic Analysis of Peroxisome Proliferator-activated Receptor γ Coactivators 1α and 1β (PGC-1α and PGC-1β) in Muscle Cells*

Peroxisome proliferator-activated receptor γ coactivator (PGC)-1α is a coactivator of nuclear receptors and other transcription factors that regulates several components of energy metabolism, particularly certain aspects of adaptive thermogenesis in brown fat and skeletal muscle, hepatic gluconeogenesis, and fiber type switching in skeletal muscle. PGC-1α has been shown to induce mitochondrial biogenesis when expressed in muscle cells, and preliminary analysis has suggested that this molecule may specifically increase the fraction of uncoupled versus coupled respiration. In this paper, we have performed detailed bioenergetic analyses of the function of PGC-1α and its homolog PGC-1β in muscle cells by monitoring simultaneously oxygen consumption and membrane potential. Cells expressing PGC-1α or PGC-1β display higher proton leak rates at any given membrane potential than control cells. However, cells expressing PGC-1α have a higher proportion of their mitochondrial respiration linked to proton leak than cells expressing PGC-1β. Although these two proteins cause a similar increase in the expression of many mitochondrial genes, PGC-1β preferentially induces certain genes involved in the removal of reactive oxygen species, recently recognized as activators of uncoupling proteins. Together, these data indicate that PGC-1α and PGC-1β profoundly alter mitochondrial metabolism and suggest that these proteins are likely to play different physiological functions.