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.
| Original language | English (US) |
|---|---|
| Article number | 1243417 |
| Journal | Science |
| Volume | 342 |
| Issue number | 6158 |
| DOIs | |
| State | Published - Jan 1 2013 |
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Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. / Bien, Clara; Affinati, Alison H.; Ramsey, Kathryn M; Kuo, Hsin Yu; Yu, Wei; Sena, Laura A.; Ilkayeva, Olga; Marcheva, Biliana; Kobayashi, Yumiko; Omura, Chiaki; Levine, Daniel C.; Bacsik, David J.; Gius, David R; Newgard, Christopher B.; Goetzman, Eric; Chandel, Navdeep; Denu, John M.; Mrksich, Milan; Bass, Joseph.
In: Science, Vol. 342, No. 6158, 1243417, 01.01.2013.Research output: Contribution to journal › Article
TY - JOUR
T1 - Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice
AU - Bien, Clara
AU - Affinati, Alison H.
AU - Ramsey, Kathryn M
AU - Kuo, Hsin Yu
AU - Yu, Wei
AU - Sena, Laura A.
AU - Ilkayeva, Olga
AU - Marcheva, Biliana
AU - Kobayashi, Yumiko
AU - Omura, Chiaki
AU - Levine, Daniel C.
AU - Bacsik, David J.
AU - Gius, David R
AU - Newgard, Christopher B.
AU - Goetzman, Eric
AU - Chandel, Navdeep
AU - Denu, John M.
AU - Mrksich, Milan
AU - Bass, Joseph
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84884248040&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884248040&partnerID=8YFLogxK
U2 - 10.1126/science.1243417
DO - 10.1126/science.1243417
M3 - Article
VL - 342
JO - Science
JF - Science
SN - 0036-8075
IS - 6158
M1 - 1243417
ER -