[HTML][HTML] Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival

H Yang, T Yang, JA Baur, E Perez, T Matsui… - Cell, 2007 - cell.com
H Yang, T Yang, JA Baur, E Perez, T Matsui, JJ Carmona, DW Lamming, NC Souza-Pinto
Cell, 2007cell.com
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 …
Summary
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.
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