RRC ID 47273
著者 Klemz R, Reischl S, Wallach T, Witte N, Jürchott K, Klemz S, Lang V, Lorenzen S, Knauer M, Heidenreich S, Xu M, Ripperger JA, Schupp M, Stanewsky R, Kramer A.
タイトル Reciprocal regulation of carbon monoxide metabolism and the circadian clock.
ジャーナル 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.
巻・号 24(1)
ページ 15-22
公開日 2017-1-1
DOI 10.1038/nsmb.3331
PII nsmb.3331
PMID 27892932
MeSH ARNTL Transcription Factors / metabolism Animals CLOCK Proteins / metabolism Carbon Monoxide / metabolism* Cell Line, Tumor Circadian Clocks* Drosophila melanogaster Glucose / metabolism Heme / metabolism Heme Oxygenase (Decyclizing) / physiology Homeostasis Humans Male Metabolic Networks and Pathways Mice, Inbred C57BL Mice, Knockout Motor Activity Protein Binding Transcription, Genetic Transcriptional Activation
IF 11.98
引用数 16
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY BIOPHYSICS CELL BIOLOGY
リソース情報
ショウジョウバエ 14716R-1 14716R-3