Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice

Science. 2013 Nov 1;342(6158):1243417. doi: 10.1126/science.1243417. Epub 2013 Sep 19.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • Acetylation
  • Animals
  • Circadian Clocks / genetics
  • Circadian Clocks / physiology*
  • Energy Metabolism*
  • Fasting
  • Lipid Metabolism
  • Liver / metabolism
  • Mice
  • Mice, Knockout
  • Mitochondria, Liver / metabolism*
  • NAD / metabolism*
  • Oxidation-Reduction
  • Oxygen Consumption
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism

Substances

  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Sirt3 protein, mouse
  • NAD
  • Sirtuin 3