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