MISO通过建立膜子域来调节线粒体动力学和mtDNA稳态
Yue Zhang1, Yuchen Xia1, Xinhui Wang1
1The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Nature cell biology
|December 15, 2025
概括
MISO蛋白组织专门的线粒体 (SMEM),以保持线粒体DNA (mtDNA) 的健康. 内部线粒体应激稳定了MISO,触发了SMEM组装和mtDNA降解.
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
- 分子机制的分子机制
背景情况:
- 线粒体动力学和mtDNA稳态对于细胞功能至关重要.
- 专门的线粒体子域,小MTFP1丰富的线粒体 (SMEM),是涉及的,但不太了解.
- SMEM形成的分子调节剂及其在mtDNA维护中的作用尚不清楚.
研究的目的:
- 识别和描述控制SMEM形成的分子机制.
- 阐明MISO在调节线粒体动力学和mtDNA稳态中的作用.
- 了解内部线粒体膜压力如何影响SMEM组装.
主要方法:
- 确定了MISO (线粒体内膜子域组织者) 作为一个关键的调节器.
- 使用了Drosophila和哺乳动物细胞模型.
- 通过基因剥离和蛋白质相互作用研究,研究了MISO在线粒体融合/裂变和SMEM生物发生中的作用.
- 分析了线粒体内膜应力对MISO稳定性和SMEM形成的影响.
主要成果:
- 通过抑制融合 (通过MTFP1) 和促进裂变 (通过FIS1-DRP1) 来调节线粒体动力学.
- MISO对于SMEM生物发生是必不可少的并且足够的,并促进它们的外围裂变,从而降解mtDNA.
- 内部线粒体膜的压力 (mtDNA损伤,OXPHOS功能障碍,晶状体的破坏) 稳定了MISO,启动了SMEM组装.
- 在压力诱导的SMEM组件中,MISO的C端域和寡合化是至关重要的.
结论:
- MISO是一种保存的蛋白质,可以调节SMEM形成和线粒体动力学.
- MISO充当了内线粒体膜压力和mtDNA稳态之间的关键联系.
- 这项研究揭示了一种新的分子途径,通过依赖MISO的SMEM组织来调节线粒体质量控制.
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