Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jan;24(1):15-22.
doi: 10.1038/nsmb.3331. Epub 2016 Nov 28.

Reciprocal Regulation of Carbon Monoxide Metabolism and the Circadian Clock

Affiliations

Reciprocal Regulation of Carbon Monoxide Metabolism and the Circadian Clock

Roman Klemz et al. Nat Struct Mol Biol. .

Abstract

Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Feedback of metabolic signals, such as redox state, NAD+/NADH and AMP/ADP ratios, or heme, modulate circadian rhythms and thereby optimize energy utilization across the 24-h cycle. We show that rhythmic heme degradation, which generates the signaling molecule carbon monoxide (CO), is required for normal circadian rhythms as well as circadian metabolic outputs. CO suppresses circadian transcription by attenuating CLOCK-BMAL1 binding to target promoters. Pharmacological inhibition or genetic depletion of CO-producing heme oxygenases abrogates normal daily cycles in mammalian cells and Drosophila. In mouse hepatocytes, suppression of CO production leads to a global upregulation of CLOCK-BMAL1-dependent circadian gene expression and dysregulated glucose metabolism. Together, our findings show that CO metabolism is an important link between the basic circadian-clock machinery, metabolism and behavior.

Similar articles

See all similar articles

Cited by 8 articles

See all "Cited by" articles

References

    1. Curr Biol. 2011 May 10;21(9):719-29 - PubMed
    1. Annu Rev Pharmacol Toxicol. 2006;46:411-49 - PubMed
    1. J Neurosci. 2009 Feb 25;29(8):2597-610 - PubMed
    1. PLoS One. 2012;7(2):e30722 - PubMed
    1. Biochem J. 2012 Mar 1;442(2):303-10 - PubMed

Publication types

MeSH terms

LinkOut - more resources

Feedback