Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice.
Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice.
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DOI:
10.1126/science.1243417
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发表时间:
2013-11-01
期刊:
影响因子:
--
通讯作者:
Bass J
中科院分区:
文献类型:
--
作者:
Peek CB;Affinati AH;Ramsey KM;Kuo HY;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 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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64.8
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DOI:
10.1126/science.1171641
发表时间:
2009-05-01
期刊:
Science (New York, N.Y.)
影响因子:
--
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通讯作者:
Bass J