博拉3和NFU1将线粒体铁硫集组与多个线粒体功能障碍综合征联系起来
Hui Zhong1, Alexandre Janer2, Oleh Khalimonchuk3,4
1Department of Biochemistry and Molecular Biology. University of Miami Miller School of Medicine, 1600 NW 10thAve. Miami, FL 33136, USA.
Nucleic acids research
|October 12, 2023
概括
人类线粒体核糖体使用铁硫集群进行组装和功能. 这些集群对线粒体蛋白质合成至关重要,并且与线粒体功能障碍疾病有关.
科学领域:
- 线粒体生物学 线粒体生物学
- 分子遗传学 分子遗传学
- 生物化学 生物化学
背景情况:
- 人类线粒体核糖体有三个 [2Fe-2S] 集群,组合和功能不明.
- 它们在线粒体和代谢疾病中的作用尚不清楚.
研究的目的:
- 阐明人类线粒体核糖体中的 [2Fe-2S] 集群的组装途径和功能.
- 为了研究这些集群和线粒体疾病之间的联系.
主要方法:
- 结构功能相关性研究.
- 在静止Fe-S集群生物合成/传递因子时分析线粒体稳定性.
- 检查线粒体功能障碍综合征患者的纤维细胞.
主要成果:
- [2Fe-2S]集群在线粒体组装中起着结构性的作用.
- 线粒体通过GLRX5-BOLA3节点接收 [2Fe-2S] 集群.
- 含有 [4Fe-4S] 集群的 METTL17 对于小子单元组装至关重要,可能通过 ISCA1-NFU1 节点.
- 在BOLA3或NFU1的突变导致线粒体蛋白质合成衰减.
- 线粒体 [2Fe-2S] 和 METTL17 的 [4Fe-4S] 体感知氧化还原变化,调节蛋白质合成.
结论:
- GLRX5-BOLA3和ISCA1-NFU1节点对于线粒体的铁硫集群输送至关重要.
- 这些通路的缺陷导致线粒体功能障碍综合征.
- 线粒体铁硫集群在蛋白质合成中具有结构性和调节性作用.
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