线粒体翻译需要依赖叶酸的tRNA甲基化
Raphael J Morscher1,2, Gregory S Ducker1,2, Sophia Hsin-Jung Li3
1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Nature
|January 25, 2018
概括
线粒体叶酸代谢,特别是血清甲基转移酶2 (SHMT2),对于修改线粒体tRNA至关重要. 这种tRNA修饰对于精确的蛋白质合成和通过氧化酸化的细胞能量产生至关重要.
科学领域:
- 生物化学
- 分子生物学
- 细胞代谢
背景情况:
- 叶酸对单碳代谢至关重要,对生物合成途径至关重要.
- 线粒体叶酸酶在增殖细胞和癌症中受到上调.
- 线粒体叶酸在细胞功能中的确切作用尚未完全理解.
研究的目的:
- 研究线粒体叶酸代谢在细胞功能中的特定作用.
- 确定线粒体叶酸酶活性受损对细胞过程的影响.
- 阐明线粒体叶酸影响能量代谢的机制.
主要方法:
- 产生的缺乏血清甲基转移酶2 (SHMT2) 活性的人类细胞.
- 使用线粒体核糖体分析来分析翻译.
- 评估氧化化和呼吸链酶的表达.
主要成果:
- 减少SHMT2活动会影响线粒体转化和氧化酸化.
- SHMT2产生5,10-甲基基叶酸,提供用于tRNA修饰的甲基捐赠体 (氨基氨酸).
- 缺陷的tRNA修饰导致核糖体在特定的密码体中停滞,损害呼吸酶的表达.
结论:
- 哺乳动物线粒体利用叶酸衍生的单碳单位进行tRNA甲基化.
- 这种tRNA修饰对于精确的线粒体翻译和氧化酸化至关重要.
- 叶酸代谢或SHMT2功能的干扰会对细胞能量产生负面影响.
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