Bcl-xL的内质网膜池通过依赖IP3R的释放来防止细胞死亡
Rudy Gadet1, Lea Jabbour1, Trang Thi Minh Nguyen1
1Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon, 28 rue Laennec, 69008, Lyon, France.
Cell death discovery
|August 1, 2024
概括
在癌细胞中发现的Bcl-xL蛋白具有双重作用. 它调节线粒体的亡,并控制从内分泌网膜 (ER) 释放的,防止ER应激期间的细胞死亡.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 细胞灭亡对于细胞稳定至关重要,Bcl-xL蛋白调节了内在线粒体通路.
- Bcl-xL在癌症中过度表达,并局部化到线粒体和内分泌网膜 (ER).
- 在ER的Bcl-xL的生物学意义仍然不清楚.
研究的目的:
- 调查线粒体和ER局部化的Bcl-xL的不同功能作用.
- 阐明ER局部Bcl-xL对细胞反应,特别是ER应激反应的贡献.
主要方法:
- 基因改造小鼠的产生,在ER (ER-xL) 或线粒体 (Mt-xL) 中表达Bcl-xL.
- 在这些小鼠的小鼠胚胎纤维细胞 (MEF) 上进行细胞死亡测定.
- 测量由1,4,5-伊诺西托三酸盐受体 (IP3R) 介导的ER释放.
主要成果:
- ER-xL MEFs对亡性刺激的脆弱性增加,但对ER压力的抵抗力增加.
- ER-xL MEFs显示了IP3R介导的从ER释放的减少.
- 在ER的Bcl-xL负面调节流量,防止ER耗尽,减轻未折叠蛋白反应 (UPR) 和细胞死亡.
结论:
- Bcl-xL具有双重亚细胞局部,在线粒体和ER具有不同的功能.
- 通过调节信号传递,ER局部化的Bcl-xL在管理ER压力方面发挥着至关重要的作用.
- 这项研究揭示了Bcl-xL在ER的新"月光"功能,超出了它在亡中的正规作用.
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