Circadian Clock NAD+ Cycle Drives Mitochondrial Oxidative Metabolism in Mice

被引：503

作者：

Peek, Clara Bien ^{[1
,2
]}

Nati, Alison H. Affi ^{[1
,2
]}

Ramsey, Kathryn Moynihan ^{[1
,2
]}

Kuo, Hsin-Yu ^{[3
,4
]}

Yu, Wei ^{[5
,6
]}

Sena, Laura A. ^{[7
,8
]}

Ilkayeva, Olga ^{[9
,10
]}

Marcheva, Biliana ^{[1
,2
]}

Kobayashi, Yumiko ^{[1
,2
]}

Omura, Chiaki ^{[1
,2
]}

Levine, Daniel C. ^{[1
,2
]}

Bacsik, David J. ^{[1
,2
]}

Gius, David ^{[11
]}

Newgard, Christopher B. ^{[9
,10
]}

Goetzman, Eric ^{[12
]}

Chandel, Navdeep S. ^{[7
,8
]}

Denu, John M. ^{[5
,6
]}

Mrksich, Milan ^{[3
,4
]}

Bass, Joseph ^{[1
,2
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA

[2] Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA

[3] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA

[4] Northwestern Univ, Howard Hughes Med Inst, Evanston, IL 60208 USA

[5] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53715 USA

[6] Univ Wisconsin, Wisconsin Inst Discovery, Madison, WI 53715 USA

[7] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA

[8] Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA

[9] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27705 USA

[10] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Dept Med, Durham, NC 27705 USA

[11] Northwestern Univ, Feinberg Sch Med, Dept Radiat Oncol, Chicago, IL 60611 USA

[12] Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15224 USA

来源：

SCIENCE | 2013年 / 342卷 / 6158期

关键词：

FATTY-ACID OXIDATION; GENE-EXPRESSION; NICOTINAMIDE; PATHWAYS; TISSUE; ACETYLATION; PROMOTES; GLUCOSE; MOUSE; CELLS;

D O I：

10.1126/science.1243417

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：591 / +

页数：9

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