细胞内膜网Ca2+的BAX和BAK调节:亡的一个控制点
Luca Scorrano1, Scott A Oakes, Joseph T Opferman
1Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Department of Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA.
概括
亲细胞突变蛋白BAX和BAK对于通过调节内质网膜 (ER) 和线粒体中的水平来启动细胞突变至关重要. 它们的存在对于特定的细胞死亡途径至关重要.
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:
- BAX和BAK是参与启动线粒体功能障碍的关键前性蛋白质.
- 这些蛋白质也局部化到内质网膜 (ER),表明超出线粒体的作用.
研究的目的:
- 研究BAX和BAK在调节ER平衡中的作用及其对亡的影响.
- 确定BAX和BAK局部化如何影响对不同亡刺激的敏感性.
主要方法:
- 使用了缺少BAX和BAK (DKO细胞) 的小鼠胚胎纤维细胞.
- 评估ER度 ([Ca2+]er) 和线粒体吸收.
- 恢复了SERCA表达,以纠正的失调.
- 研究了使用各种药物的亡诱导,包括从细胞内储存和BH3-only信号中释放的药物.
- 检查了ER释放和线粒体BAX/BAK对亡的要求.
主要成果:
- DKO细胞显示休息[Ca2+]er减少和线粒体吸收受损.
- SERCA表达恢复了[Ca2+]er和线粒体吸收,使DKO细胞对某些亡刺激重新敏感.
- 将BAX准线粒体恢复了只对BH3-only信号的亡.
- 许多内在的亡信号都需要ER释放和线粒体BAX/BAK.
结论:
- BAX 和 BAK 作为 ER 和线粒体中特定的亡信号的关键通道.
- 通过BAX和BAK对ER的调节对于在应对某些细胞应力时启动细胞亡至关重要.
- BAX和BAK的定位决定了它们在调解明显的亡途径中的作用.
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