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Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice.

Publication ,  Journal Article
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 ...
Published in: Science
November 1, 2013

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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Published In

Science

DOI

EISSN

1095-9203

Publication Date

November 1, 2013

Volume

342

Issue

6158

Start / End Page

1243417

Location

United States

Related Subject Headings

  • Sirtuin 3
  • Oxygen Consumption
  • Oxidation-Reduction
  • NAD
  • Mitochondria, Liver
  • Mice, Knockout
  • Mice
  • Liver
  • Lipid Metabolism
  • General Science & Technology
 

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Peek, C. B., Affinati, A. H., Ramsey, K. M., Kuo, H.-Y., Yu, W., Sena, L. A., … Bass, J. (2013). Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science, 342(6158), 1243417. https://doi.org/10.1126/science.1243417
Peek, Clara Bien, Alison H. Affinati, Kathryn Moynihan Ramsey, Hsin-Yu Kuo, Wei Yu, Laura A. Sena, Olga Ilkayeva, et al. “Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice.Science 342, no. 6158 (November 1, 2013): 1243417. https://doi.org/10.1126/science.1243417.
Peek CB, Affinati AH, Ramsey KM, Kuo H-Y, Yu W, Sena LA, et al. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science. 2013 Nov 1;342(6158):1243417.
Peek, Clara Bien, et al. “Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice.Science, vol. 342, no. 6158, Nov. 2013, p. 1243417. Pubmed, doi:10.1126/science.1243417.
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. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science. 2013 Nov 1;342(6158):1243417.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

November 1, 2013

Volume

342

Issue

6158

Start / End Page

1243417

Location

United States

Related Subject Headings

  • Sirtuin 3
  • Oxygen Consumption
  • Oxidation-Reduction
  • NAD
  • Mitochondria, Liver
  • Mice, Knockout
  • Mice
  • Liver
  • Lipid Metabolism
  • General Science & Technology