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内源的BAX和BAK在apoptotic线粒体上形成不同大小和组成的马赛克环
Sarah V Schweighofer1,2, Daniel C Jans2,3, Jan Keller-Findeisen1,2
1Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Translational Neuroinflammation and Automated Microscopy TNM, Göttingen, Germany.
Cell death and differentiation
|March 20, 2024
概括
过度表达的BAX和BAK蛋白在细胞灭绝过程中形成新的结构,与内源蛋白不同. 在野生型细胞中,BAK在线粒体上形成马赛克环之前BAX,支持 toroidal apoptotic pore 模型.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 亡包括BAX和BAK的寡合化,形成线粒体毛孔.
- 过度表达系统用于研究BAX和BAK动态.
- 过度表达的BAX/BAK与内源蛋白的超结构组合尚不清楚.
研究的目的:
- 调查过度表达的BAX和BAK是否形成相同的结构,并遵循与内源性蛋白质相同的等级.
- 在亡过程中描述BAX和BAK的超结构和时空动态.
主要方法:
- STED超分辨率显微镜 (活细胞和固定细胞).
- 在不朽细胞系和人类初级细胞中进行分析.
- 使用BAX/BAK单击淘汰模式.
主要成果:
- 过度表达的BAK形成了在非过度表达细胞中缺少的新型结构.
- 在野生类型细胞中,BAK在BAX之前被招募到亡孔中.
- 在单击细胞中,BAX和BAK独立地在线粒体上形成异质的马赛克环.
结论:
- 过度表达BAX/BAK可以导致非生理结构.
- 这些发现支持 toroidal apoptotic pore 模型.
- BAX和BAK表现出不同的招募动态,并在亡过程中形成复杂的环结构.
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