非细胞自主调节由线粒体ROS细胞信号传递和分化
Yipeng Du1, Lei Wang1, Lizbeth Perez-Castro2
1Department of Physiology, UT Southwestern Medical Center, Dallas, TX, USA.
The Journal of cell biology
|November 13, 2024
概括
线粒体反应性氧物种 (ROS) 通过破坏受体贩运来破坏细胞与细胞的通信. 恢复内体循环可以挽救发育缺陷,揭示出迅速的ROS反应影响信号传递.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
- 发展生物学 发展生物学
背景情况:
- 已知线粒体反应性氧物种 (ROS) 会导致细胞内损伤和基因组不稳定.
- 线粒体ROS对细胞间通信的非细胞自主作用仍然在很大程度上未被探索.
研究的目的:
- 研究 mitochondrial ROS 生产如何影响非细胞自主细胞-细胞信号传递.
- 阐明线粒体ROS在 oogenesis 期间影响受体贩运和细胞通信的分子机制.
主要方法:
- 利用实时成像观察受体定位和贩运动态.
- 研究了外囊复合体和内体细胞循环通路的作用.
- 使用基因操纵 (RAB11过度表达) 来评估救援策略.
主要成果:
- 线粒体ROS迅速抑制细胞表面受体的血局部化.
- ROS损害了外囊膜的结合,并导致缺陷的内体循环,阻碍了连接体 (例如,Notch连接体Delta) 的贩运.
- 过度表达RAB11可以挽救由ROS引起的联体贩运和发育缺陷.
- 邻近细胞的ROS生产通过Notch信号抑制触发了转录反应 (生长,迁移,ECM重塑).
结论:
- 线粒体功能障碍迅速影响通过ROS的非细胞自主细胞-细胞信号传递.
- 内体循环是一个由线粒体ROS调节的关键节点,影响受体贩运.
- 这项研究揭示了一种保存的,快速的ROS反应,将线粒体健康与细胞间通信和组织重塑联系起来.
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