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Peek, Clara Bien; Affinati, Alison H.; Ramsey, Kathryn Moynihan; Kuo, Hsin-Yu; Yu, Wei; Sena, Laura A.; Ilkayeva, Olga; Marcheva, Biliana; Kobayashi, Yumiko; Omura, Chiaki; Levine, Daniel C.; Bacsik, David J.; Gius, David; Newgard, Christopher B.; Goetzman, Eric; Chandel, Navdeep S.; Denu, John M.; Mrksich, Milan; Bass, Joseph
Science (American Association for the Advancement of Science), 11/2013, Letnik: 342, Številka: 6158Journal Article
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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