期刊
SCIENCE
卷 342, 期 6158, 页码 591-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1243417
关键词
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资金
- NIH/NIAMS [5P30AR057216-05]
- National Institute of Diabetes and Digestive and Kidney Diseases [F32 DK092034, F30 DK085936, T32 DK007169]
- Endocrine Society
- NIH [R01DK090242-03, P01DK58398, R01 AG038679, R01 CA152601-01, R01 CA152799-01A1, R01 CA168292-01A1, R01 CA16383801A1, 5P01HL071643-10, P01AG011412-16, R01HL097817-01, R01DK090625-01A1]
- Merck
- Janssen Pharmaceuticals
- Vanda Pharmaceuticals
- Matsutani America
- Sirtris, a GSK company
- Reset Therapeutics
Circadian clocks are self-sustained cellular oscillators that synchronize oxidative and reductive cycles in anticipation of the solar cycle. We found that the clock transcription feedback loop produces cycles of nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, adenosine triphosphate production, and mitochondrial respiration through modulation of mitochondrial protein acetylation to synchronize oxidative metabolic pathways with the 24-hour fasting and feeding cycle. Circadian control of the activity of the NAD(+)-dependent deacetylase sirtuin 3 (SIRT3) generated rhythms in the acetylation and activity of oxidative enzymes and respiration in isolated mitochondria, and NAD(+) supplementation restored protein deacetylation and enhanced oxygen consumption in circadian mutant mice. Thus, circadian control of NAD(+) bioavailability modulates mitochondrial oxidative function and organismal metabolism across the daily cycles of fasting and feeding.
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