Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1
Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1
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DOI：
10.1016/s0092-8674(00)80611-x
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发表时间：
1999-07-09
期刊：
影响因子：
64.5
通讯作者：
Spiegelman, BM
中科院分区：
文献类型：
--
作者：
Wu, ZD;Puigserver, P;Spiegelman, BM
在真核生物中，线粒体的数量和功能会因外界刺激而改变。虽然几个转录/复制因子直接调节线粒体基因，但这些因子协调成一个对环境作出反应的程序尚不清楚。我们在这里展示了PGC-1，一个冷诱导的核受体辅助激活剂，通过诱导解偶联蛋白2(UCP-2)和通过调节核呼吸因子(NRFs)来刺激肌肉细胞线粒体的生物发生和呼吸。PGC-1能刺激NRF-1和NRF-5基因的表达，并与线粒体转录因子A(MtTFA)启动子结合并共同激活NRF-1的转录功能，线粒体转录因子A是线粒体DNA复制/转录的直接调节因子。这些数据阐明了一条直接将外部生理刺激与线粒体生物发生和功能调节联系起来的途径。
Mitochondrial number and function are altered in response to external stimuli in eukaryotes. While several transcription/replication factors directly regulate mitochondrial genes, the coordination of these factors into a program responsive to the environment is not understood. We show here that PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling protein 2 (UCP-2) and through regulation of the nuclear respiratory factors (NRFs). PGC-1 stimulates a powerful induction of NRF-1 and NRF-5 gene expression; in addition, PGC-1 binds to and coactivates the transcriptional function of NRF-1 on the promoter for mitochondrial transcription factor A (mtTFA), a direct regulator of mitochondrial DNA replication/transcription. These data elucidate a pathway that directly links external physiological stimuli to the regulation of mitochondrial biogenesis and function.