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

• Published in: International journal of cancer Vol. 145; no. 6; pp. 1475 - 1483
• Main Authors: Luo, Xiangjian, Liao, Chaoliang, Quan, Jing, Cheng, Can, Zhao, Xu, Bode, Ann M., Cao, Ya
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15.09.2019; Wiley Subscription Services, Inc
• Subjects: Acetylation; Autophagy; Cancer; cancer metabolism; Energy metabolism; Humans; Localization; Malignancy; Medical research; Metabolism; Methylation; Mini Review; Mini Reviews; Mitochondria; Mitochondria - metabolism; Mitophagy; Neoplasms - metabolism; Organelles; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - chemistry; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; PGC‐1α; Phosphorylation; posttranslational modifications; Protein Conformation; Protein Processing, Post-Translational; Signal Transduction; Therapeutic applications; Transcription; Tumorigenesis; Ubiquitination; cancer metabolism; PGC-1α; posttranslational modifications
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.32253

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 γ coactivator 1a (PGC‐1α), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC‐1α 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‐1α. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC‐1α, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC‐1α in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC‐1α modulators. A better understanding of the elegant function of PGC‐1α in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC‐1α signaling.