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PMID: 17889652 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival.

Cell ·Vol. 130 ·No. 6 ·2007-09-21 ·Pages 1095-107

Yang H, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ, Lamming DW, Souza-Pinto NC, Bohr VA, Rosenzweig A, de Cabo R, Sauve AA, Sinclair DA

Abstract

A major cause of cell death caused by genotoxic stress is thought to be due to the depletion of NAD(+) from the nucleus and the cytoplasm. Here we show that NAD(+) levels in mitochondria remain at physiological levels following genotoxic stress and can maintain cell viability even when nuclear and cytoplasmic pools of NAD(+) are depleted. Rodents fasted for 48 hr show increased levels of the NAD(+) biosynthetic enzyme Nampt and a concomitant increase in mitochondrial NAD(+). Increased Nampt provides protection against cell death and requires an intact mitochondrial NAD(+) salvage pathway as well as the mitochondrial NAD(+)-dependent deacetylases SIRT3 and SIRT4. We discuss the relevance of these findings to understanding how nutrition modulates physiology and to the evolution of apoptosis.

MeSH Terms
Animals Apoptosis/drug effects Cell Hypoxia Cell Line Cell Nucleus/metabolism Cell Survival Cells, Cultured Cytokines/biosynthesis,metabolism Cytoplasm/metabolism Fasting/metabolism Food Deprivation Humans Methyl Methanesulfonate/toxicity Mice Mitochondria/drug effects,enzymology,metabolism,pathology Mitochondrial Proteins/genetics,metabolism Mutagens/toxicity NAD/metabolism Nicotinamide Phosphoribosyltransferase RNA Interference RNA, Small Interfering/metabolism Rats Sirtuin 3 Sirtuins/genetics,metabolism Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Transfection Up-Regulation
Chemicals
Cytokines Mitochondrial Proteins Mutagens RNA, Small Interfering NAD Methyl Methanesulfonate Nicotinamide Phosphoribosyltransferase nicotinamide phosphoribosyltransferase, human nicotinamide phosphoribosyltransferase, mouse nicotinamide phosphoribosyltransferase, rat SIRT3 protein, human Sirtuin 3 Sirtuins
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Yang Hongying
Department of Pathology, Paul F. Glenn Laboratories, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Yang Tianle
Baur Joseph A
Perez Evelyn
Matsui Takashi
Carmona Juan J
Lamming Dudley W
Souza-Pinto Nadja C
Bohr Vilhelm A
Rosenzweig Anthony
de Cabo Rafael
Sauve Anthony A
Sinclair David A
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/j.cell.2007.07.035
Published
2007-09-21
Pages
1095-107
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3366687
Subset
IM
Grants
NIA NIH HHS · P01 AG027916-030003 · United States
NIA NIH HHS · P01 AG027916-020003 · United States
NIA NIH HHS · P01 AG027916-010003 · United States
NIA NIH HHS · P01 AG027916-04S20003 · United States
NIA NIH HHS · R01AG028730 · United States
NIA NIH HHS · R01 AG019719-06A1 · United States
NIGMS NIH HHS · R01 GM068072 · United States
NIA NIH HHS · P01 AG027916 · United States
NIA NIH HHS · P01 AG027916-04S10003 · United States
NIA NIH HHS · R01 AG028730 · United States
Intramural NIH HHS · United States
NIA NIH HHS · R01 AG019719-07 · United States
NIA NIH HHS · R01 AG028730-02 · United States
NIDDK NIH HHS · R01 DK073466 · United States
NIA NIH HHS · R01 AG028730-01A1 · United States
NIGMS NIH HHS · R01GM068072 · United States
NIA NIH HHS · P01 AG027916-040003 · United States
NIA NIH HHS · R01 AG019719 · United States
NIDDK NIH HHS · R01 DK 073466 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2007.07.035 PMC Full Text View journal details
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