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Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways
Lei Yin1, Nan Wu, Joshua C Curtin
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Science (New York, N.Y.)
|November 17, 2007
Summary
Heme, an essential molecule for metabolism, binds to the Rev-erbalpha protein, a key part of the body's internal clock. This interaction helps control the circadian clock, glucose levels, and energy balance.
Area of Science:
- Biochemistry
- Molecular Biology
- Chronobiology
Background:
- The circadian clock regulates metabolic homeostasis in mammals.
- Heme is crucial for oxidative metabolism and circadian rhythmicity.
- The molecular link between heme and circadian regulation was unknown.
Purpose of the Study:
- To identify the circadian factor integrating heme's dual functions.
- To elucidate the mechanism by which heme influences circadian rhythm and metabolism.
Main Methods:
- Investigated the interaction between heme and the orphan nuclear receptor Rev-erbalpha.
- Analyzed heme's effect on Rev-erbalpha's interaction with corepressor complexes.
- Assessed heme's impact on hepatic gluconeogenic gene expression and glucose output.
Main Results:
- Heme binds reversibly to Rev-erbalpha, a core circadian clock component.
- Heme binding modulates Rev-erbalpha's interaction with nuclear receptor corepressor complexes.
- Heme suppresses hepatic gluconeogenic gene expression and glucose production via Rev-erbalpha.
Conclusions:
- Rev-erbalpha functions as a heme sensor.
- This heme-sensing mechanism coordinates the cellular clock, glucose homeostasis, and energy metabolism.
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