Laboratory of Metabolism and Obesity, Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, Spain; CIBERDEM (CIBER de Diabetes y Enfermedades Metabólicas Asociadas), Instituto de Salud Carlos III, Barcelona, Spain.
FEBS J. 2015 Feb;282(4):647-72. doi: 10.1111/febs.13175. Epub 2015 Jan 12.
Members of the PGC-1 family of coactivators have been revealed as key players in the regulation of energy metabolism. Early gain- and loss-of-function studies led to the conclusion that all members of the PGC-1 family (PGC-1α, PGC-1β and PRC) play redundant roles in the control of mitochondrial biogenesis by regulating overlapping gene expression programs. Regardless of this, all PGC-1 coactivators also appeared to differ in the stimuli to which they respond to promote mitochondrial gene expression. Although PGC-1α was found to be induced by different physiological or pharmacological cues, PGC-1β appeared to be unresponsive to such stimuli. Consequently, it has long been widely accepted that PGC-1α acts as a mediator of mitochondrial biogenesis induced by cues that signal high-energy needs, whereas the role of PGC-1β is restricted to the maintenance of basal mitochondrial function. By contrast, the function of PRC appears to be restricted to the regulation of gene expression in proliferating cells. However, recent studies using tissue-specific mouse models that lack or overexpress different PGC-1 coactivators have provided emerging evidence not only supporting new roles for PGC-1s, but also redefining some of the paradigms related to the precise function and mode of action of PGC-1 coactivators in mitochondrial biogenesis. The present review discusses some of the new findings regarding the control of mitochondrial gene expression by PGC-1 coactivators in a tissue-specific context, as well as newly-uncovered functions of PGC-1s beyond mitochondrial biogenesis, and their link to pathologies, such as diabetes, muscular dystrophies, neurodegenerative diseases or cancer.
PGC-1 家族共激活因子成员已被揭示为调节能量代谢的关键因子。早期的增益和缺失功能研究得出结论，PGC-1 家族的所有成员（PGC-1α、PGC-1β 和 PRC）通过调节重叠的基因表达程序，在控制线粒体生物发生方面发挥冗余作用。尽管如此，所有 PGC-1 共激活因子似乎也在它们响应以促进线粒体基因表达的刺激方面存在差异。虽然发现 PGC-1α 被不同的生理或药理学线索诱导，但 PGC-1β 似乎对这些线索没有反应。因此，长期以来，人们普遍认为 PGC-1α 作为由高能量需求信号诱导的线粒体生物发生的介质起作用，而 PGC-1β 的作用仅限于维持基础线粒体功能。相比之下，PRC 的功能似乎仅限于调节增殖细胞中的基因表达。然而，最近使用组织特异性缺乏或过表达不同 PGC-1 共激活因子的小鼠模型进行的研究不仅提供了支持 PGC-1 发挥新作用的新证据，而且还重新定义了与 PGC-1 共激活因子在线粒体生物发生中的精确功能和作用模式相关的一些范例。本综述讨论了在组织特异性背景下 PGC-1 共激活因子对线粒体基因表达的控制的一些新发现，以及 PGC-1s 超越线粒体生物发生的新功能，以及它们与病理学（如糖尿病、肌肉营养不良、神经退行性疾病或癌症）的联系。
