期刊
SCIENCE
卷 318, 期 5857, 页码 1786-1789出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1150179
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资金
- NIDDK NIH HHS [R01 DK45586] Funding Source: Medline
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-erb alpha, 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-erb alpha-mediated gene repression. Thus, Rev-erb alpha serves as a heme sensor that coordinates the cellular clock, glucose homeostasis, and energy metabolism.
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