TIM22载体转位酶通过促进线粒体对Fe-S生物生成的铁吸收来支持细胞增殖
Shuai Liu1, Qingyu Li2, Mengye Cao3
1State Key Laboratory of Molecular Oncology, School of Basic Medical Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
线粒体使用TIM22复合体进口铁,这对于铁-硫 (Fe-S) 生物发生至关重要. 这一发现揭示了线粒体在细胞建设过程中的关键作用.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生化学
- 遗传学 是一个遗传学.
背景情况:
- 线粒体对于细胞代谢至关重要,通过与细胞质交换代谢物来支持生物合成.
- 线粒体铁硫 (Fe-S) 生物发生对于细胞功能至关重要,其失调导致遗传性疾病.
- 哺乳动物细胞中Fe-S生物发生的精确调节尚未完全理解.
研究的目的:
- 研究调节线粒体铁硫 (Fe-S) 生物发生在哺乳动物细胞中的机制.
- 通过基因查,识别涉及Fe-S集群生物发生的新型因素.
- 阐明TIM22复合体在线粒体铁代谢和Fe-S生物生成中的作用.
主要方法:
- 以线粒体为重点的CRISPR查被用于识别Fe-S生物发生所必需的基因.
- 基于DepMap的基因共同关键性分析被用来找到功能相关的基因.
- 实验包括评估铁载体水平,线粒体铁吸收,Fe-S生物发生,细胞增殖和斑马鱼胚胎发育.
主要成果:
- 发现TIM22复合物的组成部分,包括TIMM29,对于Fe-S生物发生是有选择性的.
- 丧失TIM22复合体的功能导致线粒体铁载体的存在减少,铁的吸收受损.
- 恢复线粒体铁水平挽救了TIMM29缺乏细胞中的Fe-S生物发生和细胞增殖,并挽救了斑马鱼的发育.
结论:
- TIM22载体转位酶在促进导体介导的铁吸收到线粒体中发挥着关键作用.
- 这种铁的吸收对于线粒体铁硫 (Fe-S) 生物发生是必不可少的.
- 线粒体通过Fe-S集群生产在细胞合成中发挥直接的生物合成作用.
更多相关视频
07:17Improving the Accuracy of Flow Cytometric Assessment of Mitochondrial Membrane Potential in Hematopoietic Stem and Progenitor Cells Through the Inhibition of Efflux Pumps
Published on: July 30, 2019
11:13MitoCeption: Transferring Isolated Human MSC Mitochondria to Glioblastoma Stem Cells
Published on: February 22, 2017
相关概念视频
Protein Transport into the Inner Mitochondrial Membrane
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Mitochondrial Protein Sorting
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Energy to Drive Translocation
Generally, polypeptides are unfolded by two distinct...
The ADP/ATP Carrier Protein
The Early Endosome: Endocytosis of Transferrin
