Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators of many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, and inflammation. Accumulating evidence has shown that PGC-1s are implicated in many diseases, such as cancers, cardiac diseases and cardiovascular diseases, neurological disorders, kidney diseases, motor system diseases, and metabolic disorders. Examining the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of PGC-1s. Furthermore, discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention methods. In this review, we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network, discuss the physio-pathological roles of PGC-1s in human diseases, review the application of PGC-1s, including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies, and suggest several directions for future investigations. This review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.

过氧化物酶体增殖物激活受体γ共激活因子-1 (PGC-1) 家族 (PGC-1s) 由三个成员组成，包括 PGC-1α、PGC-1β 和 PGC-1 相关共激活因子 (PRC)，被发现超过四分之一世纪前。PGC-1 是许多重要细胞事件的重要协调者，包括线粒体功能、氧化应激、内质网稳态和炎症。越来越多的证据表明，PGC-1与许多疾病有关，如癌症、心脏病和心血管疾病、神经系统疾病、肾脏疾病、运动系统疾病和代谢紊乱。检查 PGC-1 的上游调节剂和共激活伙伴并识别 PGC-1 下游效应器调节的关键生物事件有助​​于呈现 PGC-1 的复杂网络。此外，探讨PGC-1与疾病的相关性以及总结针对PGC-1的治疗有助于制定个体化、精准的干预方法。本文综述了PGC-1家族及其分子调控网络的基础知识，讨论了PGC-1在人类疾病中的生理病理作用，综述了PGC-1的应用，包括诊断和预后价值。临床前研究中 PGC-1 和几种疗法的研究，并提出了未来研究的几个方向。本综述展示了靶向 PGC-1 在疾病治疗中的巨大潜力，并有望促进 PGC-1 作为新治疗靶点的推广。