线粒体亡诱导因子的分子表征
S A Susin1, H K Lorenzo, N Zamzami
1Centre National de la Recherche Scientifique, UPR 420, Villejuif, France.
Nature
|February 16, 1999
概括
线粒体含有一种新型的诱导细胞亡因子 (AIF),可触发细胞死亡. 这种蛋白质转移到核中,导致DNA碎片化和染色质凝聚,独立于caspases.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 线粒体是细胞亡的中央调节者.
- 关键的细胞亡调节蛋白位于线粒体膜间空间.
- 这些蛋白质被释放以启动细胞死亡级联.
研究的目的:
- 从线粒体中识别和描述一种新型的诱导亡因子 (AIF).
- 阐明AIF诱导亡的机制.
- 确定AIF作为细胞死亡中的线粒体效应因子的作用.
主要方法:
- 对AIF基因的识别和克隆.
- 再组合AIF的表达方式.
- 在实验室测试中使用孤立的核和线粒体.
- 在完整的细胞中微注射AIF.
- 评估酶依赖和独立途径.
主要成果:
- AIF是一种57,000MW的黄蛋白,与细菌氧化还原酶相同.
- 再组合AIF在孤立的核中诱导染色质凝聚和DNA碎片化.
- 通过AIF,可以从纯化的线粒体中释放细胞染色体c和caspase-9.
- 在完整的细胞中,AIF会诱导类似于亡的变化,独立于酶活性.
- 过度表达Bcl-2抑制了AIF的释放,但并没有抑制其亡活性.
结论:
- AIF是一种新型的线粒体蛋白质,可以直接诱导亡.
- AIF作为线粒体效应剂,转移到细胞核,触发细胞死亡.
- AIF介导的亡是独立于酶途径的.
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