对营养素敏感的线粒体NAD+水平决定了细胞存活率
Hongying Yang1, Tianle Yang, Joseph A Baur
1Department of Pathology, Paul F. Glenn Laboratories, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Cell
|September 25, 2007
概括
线粒体尼古丁胺胺氨基二核酸 (NAD+) 保护细胞免受基因毒性压力,即使核NAD+耗尽. 禁食通过酶Nampt增加了这种保护性线粒体NAD +.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
背景情况:
- 基因毒性压力往往会导致细胞死亡,原因是尼古丁胺胺二核酸 (NAD+) 的耗尽.
- NAD+对于细胞能量代谢和信号通路至关重要.
- 线粒体在细胞生存和能量生产中发挥着至关重要的作用.
研究的目的:
- 研究线粒体NAD+在基因毒性压力下细胞存活中的作用.
- 探索禁食对NAD+水平和细胞活力的影响.
- 为了确定关键的酶和途径,涉及维护线粒体NAD+平衡.
主要方法:
- 细胞模型中的基因毒性应激诱导.
- 在核,细胞质和线粒体内测量NAD+水平.
- 尼古丁胺酸基转移酶 (Nampt) 酶活性的分析.
- 对线粒体NAD+救援途径和素脱乙酶 (SIRT3,SIRT4) 的研究.
主要成果:
- 线粒体NAD+水平在基因毒性压力期间保持稳定,与核和细胞质池不同.
- 在动物中,禁食48小时会增加Nampt水平和线粒体NAD+.
- 升高的Nampt可以防止细胞死亡,这取决于线粒体的NAD+救援和SIRT3/SIRT4活性.
结论:
- 线粒体作为NAD+的储存库,可以在基因毒性压力期间保持细胞活力.
- 禁食诱导的Nampt上调增强了线粒体NAD+并促进了细胞生存.
- 这些发现突出了营养,NAD+代谢和细胞死亡途径之间的相互作用.
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