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Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival.

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.

SUBMITTER: Yang H

PROVIDER: S-EPMC3366687 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival.

Yang Hongying H Yang Tianle T Baur Joseph A JA Perez Evelyn E Matsui Takashi T Carmona Juan J JJ Lamming Dudley W DW Souza-Pinto Nadja C NC Bohr Vilhelm A VA Rosenzweig Anthony A de Cabo Rafael R de Cabo Rafael R Sauve Anthony A AA Sinclair David A DA

Cell 20070901 6

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 prov ...[more]

PMID: 17889652

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