核DNA损伤触发的ATM依赖AMPK激活调节了线粒体辐射反应
Tsutomu Shimura1, Kenta Sunaga2, Mayu Yamazaki2
1Department of Environmental Health, National Institute of Public Health Wako, Saitama, Japan.
International journal of radiation biology
|January 3, 2024
概括
AMP激活蛋白激酶 (AMPK) 激活途径因压力而异. 辐射触发了ATM依赖的信号,而缺氧和葡萄糖饥饿则独立于ATM激活了AMPK,影响了线粒体平衡.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体功能 线粒体功能
- 信号传导传导是指信号的传导.
背景情况:
- AMP激活蛋白激酶 (AMPK) 是一个关键的细胞能量传感器.
- 在维护线粒体平衡中,AMPK起着至关重要的作用.
- 在压力下了解AMPK激活机制对于细胞健康至关重要.
研究的目的:
- 研究AMPK激活的调控机制.
- 阐明响应细胞应激的细胞内信号通路.
- 确定负责AMPK激活的上游激酶.
主要方法:
- 使用了正常和ATM缺乏的人类纤维细胞.
- 使用ATM,DNA-PK和AKT的抑制剂.
- 通过免疫染色和西式涂抹检查了蛋白质表达.
主要成果:
- 辐射诱导的DNA损伤激活了ATM依赖的AMPK信号,用于线粒体质量控制.
- 低氧和葡萄糖饥饿通过ATP枯竭激活AMPK,独立于ATM.
- DNA-PK和AKT没有参与AMPK介导的线粒体信号传递.
结论:
- AMPK激活途径是刺激依赖的.
- 辐射通过LKB1 (ATP耗尽) 和ATM (DNA损伤) 途径激活AMPK.
- 核DNA损伤向线粒体发送信号是辐射后细胞命运的关键.
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