Reciprocal regulation of carbon monoxide metabolism and the circadian clock
- Klemz, Roman Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
- Reischl, Silke Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
- Wallach, Thomas Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
- Witte, Nicole Institute of Pharmacology, Center for Cardiovascular Research CCR, Charité Universitätsmedizin Berlin, Germany
- Jürchott, Karsten Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
- Klemz, Sabrina Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
- Lang, Veronika Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
- Lorenzen, Stephan Bernhard-Nocht-Institut, Hamburg, Germany
- Knauer, Miriam Institute of Pharmacology, Center for Cardiovascular Research CCR, Charité Universitätsmedizin Berlin, Germany
- Heidenreich, Steffi Institute of Pharmacology, Center for Cardiovascular Research CCR, Charité Universitätsmedizin Berlin, Germany
- Xu, Min Department of Cell and Developmental Biology, University College London, UK
- Ripperger, Jürgen A. Division of Biochemistry, Department of Biology, University of Fribourg, Switzerland
- Schupp, Michael Institute of Pharmacology, Center for Cardiovascular Research CCR, Charité Universitätsmedizin Berlin, Germany
- Stanewsky, Ralf Department of Cell and Developmental Biology, University College London, UK - Westfälische Wilhelms-Universität Münster, Germany
- Kramer, Achim Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
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01.01.2017
Published in:
- Nature Structural & Molecular Biology. - 2017, vol. 24, no. 1, p. 15-22
English
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.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Biologie
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 279084
- DOI 10.1038/nsmb.3331
- Persistent URL
- https://folia.unifr.ch/unifr/documents/305297
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