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Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival

2007; Cell Press; Volume: 130; Issue: 6 Linguagem: Inglês

10.1016/j.cell.2007.07.035

1097-4172

Hongying Yang, Tianle Yang, Joseph A. Baur, Evelyn Perez, Takashi Matsui, Juan J. Carmona, Dudley W. Lamming, Nadja C. de Souza‐Pinto, Vilhelm A. Bohr, Anthony Rosenzweig, Rafael de Cabo, Anthony A. Sauve, David Sinclair,

Autophagy in Disease and Therapy

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.