循环时钟 NAD+循环驱动小鼠中的线粒体氧化代谢
Clara Bien Peek1, Alison H Affinati, Kathryn Moynihan Ramsey
1Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Science (New York, N.Y.)
|September 21, 2013
概括
循环时钟通过控制尼古丁胺氨酸二核酸 (NAD(+)) 水平来调节日常代谢节奏. 这会影响线粒体功能和能量生产,使新陈代谢与食和禁食周期同步.
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:
- 昼夜钟是内源性振荡器,与24小时的光暗周期同步生理过程.
- 氧化和还原细胞循环对于能量代谢至关重要.
- 线粒体功能对于细胞能量生产至关重要.
研究的目的:
- 调查昼夜钟在调节NAD (+) 生物合成和线粒体氧化功能中的作用.
- 阐明将昼夜节律与代谢途径联系起来的分子机制.
- 为了确定如何昼夜控制NAD的生物可用性影响生物的新陈代谢.
主要方法:
- 对昼夜转录反循环的分析.
- 测量尼古丁胺胺氨基二核酸 (NAD(+)) 生物合成和腺三酸盐 (ATP) 生产.
- 评估线粒体蛋白质乙化和呼吸.
- 在孤立的线粒体和昼夜突变小鼠中进行的研究.
- 在NAD () 补充实验中.
主要成果:
- 昼夜时钟调节循环NAD生物合成,ATP生产和线粒体呼吸.
- 线粒体蛋白质乙化循环调节同步氧化代谢与食禁食周期.
- 循环控制NAD (((+) 依赖的脱乙酶3 (SIRT3) 驱动酶活性和线粒体呼吸的节奏.
- 在突变的小鼠中,NAD ((+) 补充恢复了脱乙和增加了氧气消耗.
结论:
- 循环时钟同步细胞氧化代谢与日常食和禁食模式.
- 循环控制NAD的生物可用性是调节线粒体氧化功能的一个关键机制.
- 这种调节会影响整个日间循环的生物代谢.
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