染色体的稳定性保证了线粒体的稳定性,并防止了mTORC1的过度激活
Vinoth Sigamani1, Mohd Yousuf1, Daniel L Johnson2
1Department of Pathology and Laboratory Medicine, College of Medicine and the Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, United States of America.
染色质的稳定性对于细胞适应营养变化至关重要. 保持基因素H3 lysine 37 (H3K37) 稳定性可以防止mTORC1信号和有毒线粒体应激.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细胞通过调节染色体和基因表达来适应营养的流动.
- 拉巴胺素复合体1 (mTORC1) 途径的机械性标将营养信号与染色质调节相结合.
- 染色体稳定性在对mTORC1激活和应激适应的反中的作用尚不清楚.
研究的目的:
- 为了研究基因素H3 lysine 37 (H3K37) 依赖的染色体稳定性在应对mTORC1压力的作用.
- 为了确定染色体稳定性是否影响mTORC1信号传递和细胞适应.
- 阐明H3K37A突变在mTORC1抑制期间影响细胞平衡的机制.
主要方法:
- 利用与影响染色质稳定性的突变物 (例如,Set2,Rpd3S,基因素沉积途径) 的遗传相互作用分析.
- 进行了转录组分析,以评估基因表达变化,特别是在线粒体中.
- 研究了活性氧物种 (ROS) 和线粒体逆行信号在细胞活力的作用.
主要成果:
- 在H3K37依赖的染色体稳定性防止了基因素降解,抑制了mTORC1的信号传递,并在mTORC1压力期间保持线粒体平衡.
- H3K37A突变与染色体不稳定突变相结合,在mTORC1抑制时导致合成致命性.
- H3K37A错误调节线粒体转录组,增加ROS和激活有害的逆行信号,可以通过抑制逆行信号或中和ROS来挽救.
结论:
- 染色体的稳定性,特别是H3K37的稳定性,是对过度mTORC1活动的关键保护措施.
- 在mTORC1压力期间破坏染色质稳定导致线粒体功能障碍和细胞死亡.
- 保持染色体完整性对于预防有毒线粒体应激和确保细胞适应至关重要.
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