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.
Duke Scholars
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- Sirtuin 3
- Oxygen Consumption
- Oxidation-Reduction
- NAD
- Mitochondria, Liver
- Mice, Knockout
- Mice
- Liver
- Lipid Metabolism
- General Science & Technology
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Sirtuin 3
- Oxygen Consumption
- Oxidation-Reduction
- NAD
- Mitochondria, Liver
- Mice, Knockout
- Mice
- Liver
- Lipid Metabolism
- General Science & Technology