Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways.
Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways.
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发表时间：
2007
期刊：
影响因子：
56.9
通讯作者：
L. Yin;Nan Wu;J. Curtin;M. Qatanani;Nava R. Szwergold;R. A. Reid;G. Waitt;D. Parks;K. Pearce-K.-Pearc
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文献类型：
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作者：
L. Yin;Nan Wu;J. Curtin;M. Qatanani;Nava R. Szwergold;R. A. Reid;G. Waitt;D. Parks;K. Pearce-K.-Pearc
生物钟在时间上协调哺乳动物的代谢动态平衡。这其中的核心是血红素，这是一种含铁的卟啉，它是参与氧化代谢的酶的修复基团，也是调节昼夜节律的转录因子。整合血红素这一双重功能的昼夜节律因素尚不清楚。我们发现血红素可逆地与孤儿核受体Rev-erbalpha结合，Rev-erbalpha是昼夜节律核心时钟的关键负成分，并调节它与核受体辅阻遏物的相互作用。此外，血红素通过Rev-erbalpha介导的基因抑制抑制肝脏糖异生基因的表达和葡萄糖输出。因此，REV-ERBALPHA作为一个血红素传感器，协调细胞时钟、葡萄糖动态平衡和能量代谢。
The circadian clock temporally coordinates metabolic homeostasis in mammals. Central to this is heme, an iron-containing porphyrin that serves as prosthetic group for enzymes involved in oxidative metabolism as well as transcription factors that regulate circadian rhythmicity. The circadian factor that integrates this dual function of heme is not known. We show that heme binds reversibly to the orphan nuclear receptor Rev-erbalpha, a critical negative component of the circadian core clock, and regulates its interaction with a nuclear receptor corepressor complex. Furthermore, heme suppresses hepatic gluconeogenic gene expression and glucose output through Rev-erbalpha-mediated gene repression. Thus, Rev-erbalpha serves as a heme sensor that coordinates the cellular clock, glucose homeostasis, and energy metabolism.