来自线粒体的核ATP激增可以防止受限诱导的增殖缺陷
Ritobrata Ghose1,2,3, Fabio Pezzano1, Rémi Badia1
1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain.
Nature communications
|July 30, 2025
概括
细胞封闭导致线粒体在核附近聚集,增加核ATP. 这种适应有助于DNA修复和细胞在机械应力下增殖.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 分子生物学分子生物学
背景情况:
- 细胞微环境显著影响细胞的行为和功能.
- 机械监禁对有机细胞局部化和细胞代谢的影响仍然不太清楚.
研究的目的:
- 研究机械限制如何影响亚细胞器官分布和细胞代谢.
- 为了阐明核-线粒体在限制下接近的机制和功能后果.
主要方法:
- 蛋白质组学分析以确定细胞分数中的蛋白质丰富.
- 定量活细胞显微镜以在体外追踪有机体的动态.
- 在线粒体局部化中研究内质网膜和actin细胞骨在线粒体局部化中的作用.
- 评估核-线粒体接近对核ATP水平和细胞适应性的影响.
主要成果:
- 细胞的限制导致了核部分中线粒体蛋白质的显著丰富.
- 机械限制导致线粒体迅速重新定位到核外围.
- 这种近距离是由一个依赖于内分泌网膜的机制介导的,该机制涉及actin细胞骨架.
- 限制导致核ATP激增,影响染色质状态,DNA修复和细胞周期进展.
结论:
- 机械限制触发了一种代谢适应,涉及核与线粒体的接近.
- 这种适应促进了DNA损伤的修复和在机械应力下细胞的增殖.
- 这项研究揭示了细胞适应物理约束的新机制.
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