Mitochondrial aggregation precedes cytochrome c 1release from mitochondria during apoptosis
Mitochondrial aggregation precedes cytochrome c 1release from mitochondria during apoptosis
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DOI：
10.1038/sj.onc.1206576
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发表时间：
2003-08-28
期刊：
影响因子：
8
通讯作者：
Tsuruo, T
中科院分区：
文献类型：
--
作者：
Haga, N;Fujita, N;Tsuruo, T
线粒体在细胞凋亡信号通路中起核心作用。在暴露于凋亡刺激后，线粒体将细胞色素c释放到细胞质中并激活半胱天冬酶级联反应，导致细胞死亡。然而，细胞色素c释放的上游事件尚未完全了解。在这里，我们定量线粒体聚集原位使用一种新的激光扫描细胞术技术，并揭示线粒体聚集在细胞凋亡过程中的出芽样形状。定量分析表明caspase-3抑制剂ZEVD不能抑制线粒体聚集。此外，bcl-x（L）转染不能抑制线粒体聚集。然而，bcl-x（L）的过表达抑制细胞色素c从线粒体的释放。因此，线粒体聚集是细胞凋亡期间细胞色素c释放上游的事件。在人白血病H9细胞中没有观察到这种线粒体聚集，其中凋亡以非依赖于线粒体的方式发生。我们的研究表明，线粒体定位的变化通过细胞色素c的释放参与细胞凋亡的调节。
Mitochondria play a central role in apoptotic signaling pathways. Upon exposure to apoptotic stimuli, mitochondria release cytochrome c to the cytoplasm and activate caspase cascade leading to cell death. However, the events upstream of cytochrome c release are not fully understood. Here, we quantitate mitochondrial aggregation in situ using a novel laser scanning cytometry technique and reveal that mitochondria aggregate during apoptosis in a budding-like shape. The quantitative analysis reveals that mitochondrial aggregation is not inhibited by caspase-3 inhibitor ZEVD. Furthermore, bcl-x(L) transfection cannot suppress mitochondrial aggregation. However, overexpression of bcl-x(L) inhibits cytochrome c release from mitochondria. Therefore, mitochondrial aggregation is an event upstream of cytochrome c release during apoptosis. This mitochondrial aggregation was not observed in human leukemia H9 cells where apoptosis occurs in a mitochondria-independent fashion. Our studies imply that changes in the localization of mitochondria participate in the regulation of apoptosis through cytochrome c release.