| First Author | Peek CB | Year | 2013 |
| Journal | Science | Volume | 342 |
| Issue | 6158 | Pages | 1243417 |
| PubMed ID | 24051248 | Mgi Jnum | J:202833 |
| Mgi Id | MGI:5522595 | Doi | 10.1126/science.1243417 |
| Citation | Peek CB, et al. (2013) Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342(6158):1243417 |
| abstractText | 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. |
