Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice.
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.
Peek, CB; Affinati, AH; Ramsey, KM; Kuo, H-Y; Yu, W; Sena, LA; Ilkayeva, O; Marcheva, B; Kobayashi, Y; Omura, C; Levine, DC; Bacsik, DJ; Gius, D; Newgard, CB; Goetzman, E; Chandel, NS; Denu, JM; Mrksich, M; Bass, J
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