Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice

Clara Bien Peek, Alison H. Affinati, Kathryn Moynihan Ramsey, Hsin Yu Kuo, Wei Yu, Laura A. Sena, Olga Ilkayeva, Biliana Marcheva, Yumiko Kobayashi, Chiaki Omura, Daniel C. Levine, David J. Bacsik, David Gius, Christopher B. Newgard, Eric Goetzman, Navdeep S. Chandel, John M. Denu, Milan Mrksich, Joseph Bass

Research output: Contribution to journalArticlepeer-review

443 Scopus citations


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.

Original languageEnglish (US)
Article number1243417
Issue number6158
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

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