AI Article Synopsis
- A major cause of cell death under genotoxic stress is the depletion of NAD(+) from the nucleus and cytoplasm, but mitochondrial NAD(+) levels stay stable and support cell survival even when other NAD(+) pools are low.
- Fasting rodents for 48 hours increases the enzyme Nampt, leading to higher mitochondrial NAD(+) levels, which helps protect against cell death through the mitochondrial NAD(+) salvage pathway and the actions of SIRT3 and SIRT4.
- This research highlights the significance of nutrition in influencing physiological responses and sheds light on the evolution of programmed cell death (apoptosis).
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366687 | PMC |
| http://dx.doi.org/10.1016/j.cell.2007.07.035 | DOI Listing |
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