Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network.
Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network.
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DOI：
10.1016/j.bbamcr.2010.09.019
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Scarpulla RC
中科院分区：
文献类型：
--
作者：
Scarpulla RC
PGC-1家族由PGC-1α、PGC-1β和PRC组成，在调控线粒体生物发生和呼吸功能的转录调控网络中发挥着核心作用。这些共激活子靶向多种转录因子，包括nrf-1、nrf-2和孤儿核激素受体ERRα等。此外，它们本身也是通过染色质重塑调节基因表达的共激活和共抑制复合体的靶标。PGC-1家族成员的表达受控制新陈代谢、分化或细胞生长的细胞外信号的调控，在某些情况下，它们的活性受到能量感受器AMPK和SIRT1翻译后修饰的调节。最近对PGC-1网络许多成员的基因敲除和沉默研究揭示了广泛严重的表型，提示存在复杂的补偿相互作用或广泛整合的功能，这些功能并不是线粒体生物发生所独有的。这些结果表明，PGC-1家族在整合线粒体生物发生和能量产生与许多不同的细胞功能方面发挥着核心作用。
The PGC-1 family of regulated coactivators, consisting of PGC-1α, PGC-1β and PRC, plays a central role in a regulatory network governing the transcriptional control of mitochondrial biogenesis and respiratory function. These coactivators target multiple transcription factors including NRF-1, NRF-2 and the orphan nuclear hormone receptor, ERRα, among others. In addition, they themselves are the targets of coactivator and co-repressor complexes that regulate gene expression through chromatin remodeling. The expression of PGC-1 family members is modulated by extracellular signals controlling metabolism, differentiation or cell growth and in some cases their activities are known to be regulated by post-translational modification by the energy sensors, AMPK and SIRT1. Recent gene knockout and silencing studies of many members of the PGC-1 network have revealed phenotypes of wide ranging severity suggestive of complex compensatory interactions or broadly integrative functions that are not exclusive to mitochondrial biogenesis. The results point to a central role for the PGC-1 family in integrating mitochondrial biogenesis and energy production with many diverse cellular functions.
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