由ROS信号诱导的线粒体Sgk1表达调节了上皮细胞的更新
Yingxiang Li1, Chengdong Liu1, Luke Rolling1
1Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.
概括
线粒体对于受伤后静止细胞的重新激活至关重要. 较高的线粒体代谢和SGK1信号促进细胞循环的重新进入和上皮的更新.
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
- 再生医学是一种再生医学.
背景情况:
- 在受伤或压力后,分化的细胞可以重新进入细胞循环.
- 控制静止细胞再激活的机制在很大程度上是未知的.
研究的目的:
- 在生理学背景下研究静止细胞激活的机制.
- 为了确定参与上皮细胞更新的关键分子参与者.
主要方法:
- 利用斑马鱼模型研究上皮细胞的活性.
- 采用遗传和药理学扰动来分析线粒体功能和信号通路.
- 评估了线粒体膜潜力,活性氧物种 (ROS) 水平和蛋白质表达 (Sgk1).
主要成果:
- 重生活化的细胞表现出线粒体膜潜能增加和线粒体代谢升高.
- 线粒体新陈代谢增加导致线粒体ROS水平更高,诱导Sgk1的表达.
- 在斑马鱼中,Sgk1的遗传删除或抑制消除了表皮细胞的活性.
- ROS依赖的线粒体Sgk1表达促进了人类乳腺癌细胞的S阶段进入.
- 发现Sgk1可酸化F1Fo-ATP合成酶,协调线粒体活动和ATP合成.
结论:
- 较高的线粒体新陈代谢和ATP合成对于细胞的重新激活至关重要.
- 涉及ROS和Sgk1的保守的线粒体内信号循环调节了上皮细胞的更新.
- Sgk1在协调线粒体功能与细胞循环重新进入方面发挥着关键作用.
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