Posttranslational regulation of PGC-1α and its implication in cancer metabolism

Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator-activated receptor gamma coactivator 1a (PGC-1 alpha), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC-1 alpha are subject to dynamic and versatile posttranslational modifications including phosphorylation, ubiquitination, methylation and acetylation in response to metabolic stress and other environmental signals. In this review, we describe the structure of PGC-1 alpha. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC-1 alpha, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC-1 alpha in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC-1 alpha modulators. A better understanding of the elegant function of PGC-1 alpha in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC-1 alpha signaling.