Yang Hongying, Yang Tianle, Baur Joseph A, Perez Evelyn, Matsui Takashi, Carmona Juan J, Lamming Dudley W, Souza-Pinto Nadja C, Bohr Vilhelm A, Rosenzweig Anthony, de Cabo Rafael, Sauve Anthony A, Sinclair David A
Department of Pathology, Paul F. Glenn Laboratories, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Cell. 2007 Sep 21;130(6):1095-107. doi: 10.1016/j.cell.2007.07.035.
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.
基因毒性应激导致细胞死亡的一个主要原因被认为是细胞核和细胞质中NAD⁺的耗竭。在此我们表明，基因毒性应激后线粒体中的NAD⁺水平保持在生理水平，并且即使细胞核和细胞质中的NAD⁺池被耗尽，线粒体中的NAD⁺仍能维持细胞活力。禁食48小时的啮齿动物显示NAD⁺生物合成酶Nampt水平升高，同时线粒体NAD⁺也增加。Nampt水平升高可提供细胞死亡保护，这需要完整的线粒体NAD⁺补救途径以及线粒体NAD⁺依赖性脱乙酰酶SIRT3和SIRT4。我们讨论了这些发现对于理解营养如何调节生理以及细胞凋亡进化的相关性。
