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.
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Key words: PGC-1α, posttranslational modifications, cancer metabolism Conflict of interest: No potential conflicts of interest were disclosed. *C.L. and J.Q. contributed equally to this work Grant sponsor: The National Key Research and Development Program of China; Grant number: 2016YFC0902000; Grant sponsor: National Natural Science Foundation of China; Grant numbers: 81573014, 81874195; Grant sponsor: the Natural Science Foundation of Hunan Province; Grant number: 2016JJ2171; Grant sponsor: the Open-End Fund for the Valuable and Precision Instruments of Central South University; Grant number: CSUZC201842 DOI: 10.1002/ijc.32253 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. History: Received 10 Nov 2018; Accepted 4 Mar 2019; Online 8 Mar 2019. Correspondence to: Xiangjian Luo, Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China, E-mail: email@example.com
© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
- cancer metabolism
- posttranslational modifications