Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice

Clara Bien, Alison H. Affinati, Kathryn M Ramsey, Hsin Yu Kuo, Wei Yu, Laura A. Sena, Olga Ilkayeva, Biliana Marcheva, Yumiko Kobayashi, Chiaki Omura, Daniel C. Levine, David J. Bacsik, David R Gius, Christopher B. Newgard, Eric Goetzman, Navdeep Chandel, John M. Denu, Milan Mrksich, Joseph Bass*

*Corresponding author for this work

Research output: Contribution to journal › Article

281 Citations (Scopus)

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 languageEnglish (US)
Article number1243417
JournalScience
Volume342
Issue number6158
DOIs
StatePublished - Jan 1 2013

Fingerprint

Circadian Clocks
NAD
Acetylation
Sirtuin 3
Fasting
Respiration
Mitochondrial Proteins
Metabolic Networks and Pathways
Oxygen Consumption
Biological Availability
Mitochondria
Adenosine Triphosphate
Drive
Enzymes
Proteins

ASJC Scopus subject areas

  • General

Cite this

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. / Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. In: Science. 2013 ; Vol. 342, No. 6158.
@article{219d734a34fe4dfa82de99b957b1d645,
title = "Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice",
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.",
author = "Clara Bien and Affinati, {Alison H.} and Ramsey, {Kathryn M} and Kuo, {Hsin Yu} and Wei Yu and Sena, {Laura A.} and Olga Ilkayeva and Biliana Marcheva and Yumiko Kobayashi and Chiaki Omura and Levine, {Daniel C.} and Bacsik, {David J.} and Gius, {David R} and Newgard, {Christopher B.} and Eric Goetzman and Navdeep Chandel and Denu, {John M.} and Milan Mrksich and Joseph Bass",
year = "2013",
month = "1",
day = "1",
doi = "10.1126/science.1243417",
language = "English (US)",
volume = "342",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6158",

}

Bien, C, Affinati, AH, Ramsey, KM, Kuo, HY, Yu, W, Sena, LA, Ilkayeva, O, Marcheva, B, Kobayashi, Y, Omura, C, Levine, DC, Bacsik, DJ, Gius, DR, Newgard, CB, Goetzman, E, Chandel, N, Denu, JM, Mrksich, M & Bass, J 2013, 'Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice', Science, vol. 342, no. 6158, 1243417. https://doi.org/10.1126/science.1243417

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 -

Bien C, Affinati AH, Ramsey KM, Kuo HY, Yu W, Sena LA et al. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science. 2013 Jan 1;342(6158). 1243417. https://doi.org/10.1126/science.1243417

Access to Document