Miller Karl N, Clark Josef P, Anderson Rozalyn M
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, USA.
Curr Opin Endocr Metab Res. 2019 Mar;5:37-44. doi: 10.1016/j.coemr.2019.02.002. Epub 2019 Feb 27.
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) is a central regulator of metabolism that is poised at the intersection of myriad intracellular signaling pathways. In this brief update, we discuss regulation of PGC-1a at multiple levels, including transcriptional, post-transcriptional, and post-translational modifications. We discuss recently identified small molecule effectors of PGC-1a that offer translational potential and promise new insight into PGC-1a biology. We highlight novel mechanistic insights relating to PGC-1a's interactions with RNA to enhance transcription and potentially influence transcript processing. Finally, we place these exciting new data in the context of aging biology, offering PGC-1a as a candidate target with terrific potential in anti-aging interventions.
过氧化物酶体增殖物激活受体γ辅激活因子-1α（PGC-1α）是新陈代谢的核心调节因子，处于众多细胞内信号通路的交汇点。在本简要更新中，我们讨论了PGC-1α在多个水平的调控，包括转录、转录后和翻译后修饰。我们讨论了最近鉴定出的PGC-1α小分子效应物，它们具有转化潜力，并有望为PGC-1α生物学提供新的见解。我们强调了与PGC-1α与RNA相互作用以增强转录并可能影响转录本加工相关的新机制见解。最后，我们将这些令人兴奋的新数据置于衰老生物学的背景下，提出PGC-1α作为抗衰老干预中具有巨大潜力的候选靶点。
