分子核平衡的调节者将线粒体代谢与mtDNA表达联系起来
Nicholas J Kramer1, Gyan Prakash1, R Stefan Isaac1
1Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Nature cell biology
|September 28, 2023
概括
研究人员发现了新的基因,PREPL和NME6,对于线粒体氧化酸化 (OXPHOS) 复合体组装至关重要. 通过调节RNA水平和线粒体功能,NME6将线粒体代谢物与基因表达联系起来.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 线粒体氧化酸化 (OXPHOS) 复合体需要核和线粒体基因的协调表达.
- 这些蛋白质复合体的双重起源性质构成了重要的基因调控挑战.
- 了解OXPHOS生物生成的机制对于细胞能量生产至关重要.
研究的目的:
- 为了确定参与双源OXPHOS蛋白质协调合成的新型基因.
- 阐明在OXPHOS生物发生过程中未表征的PREPL和NME6基因的特定作用.
主要方法:
- 使用光激活细胞分类 (FACS) 进行全基因组选,对具有不平衡复杂IV子单元的突变细胞进行了选.
- 分析与线粒体脂质代谢,蛋白质合成和RNA处理相关的基因功能.
主要成果:
- 两个未表征的基因,PREPL和NME6,被确定为OXPHOS生物发生的关键基因.
- 在线粒体脂质代谢和蛋白质合成的结合点上,PREPL会影响复杂IV组合.
- 核酸二酸激酶NME6通过其NDPK域调节OXPHOS,影响线粒体RNA丰度和线粒体基因组功能.
结论:
- 在OXPHOS生物发生过程中,NME6发挥着多方面的作用,将线粒体代谢物与基因表达联系起来.
- NME6与RCC1L形成一个复合体,以维持线粒体的pyrimidine三酸盐水平,这对于线粒体RNA至关重要.
- NME6调节了线粒体调节复合体,影响了组装和RNA伪化.
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