Mitochondrial dysfunction in cell death.

描述(申请人提供)：线粒体在 细胞凋亡(程序性细胞死亡)。尤其是蛋白质的释放，如 作为细胞色素c和Smac/Diablo从线粒体膜间间隙进入 胞浆是半胱氨酸天冬氨酸酶激活的重要触发因素，进而导致 以细胞凋亡为特征的事件。在这里，我们建议研究探索 涉及线粒体的这一凋亡途径的各个方面。首先，我们解决 细胞色素c与APAF-1蛋白的相互作用，这是 Caspase-9被激活。其次，我们研究了线粒体的变化 外膜通透性的作用；在某些情况下 在半胱氨酸天冬氨酸酶被抑制的地方，这些线粒体效应可能起作用。 对细胞的死亡负责。最后，我们探索了外在的本质 线粒体膜通透性事件，特别是与其 Bid、Bax等促和抗细胞凋亡的Bcl2家族蛋白的调控 和Bclxl。

DESCRIPTION (provided by applicant): Mitochondria play a central role in apoptosis (programmed cell death). In particular, the release of proteins, such as cytochrome c and Smac/DIABLO from the mitochondrial intermembrane space into the cytosol is an important trigger for caspase activation, which in turn leads to the events characteristic of apoptosis. Here we propose studies exploring aspects of this apoptotic pathway involving mitochondria. First, we address the interaction of cytochrome c with the Apaf- 1 protein, a step required for caspase-9 activation. Second, we investigate the changes in mitochondrial function resulting from outer membrane permeabilization; under circumstances where caspases are inhibited, these mitochondrial effects may be responsible for the death of the cell. Finally, we explore the nature of the outer mitochondrial membrane permeabilization event, particularly with regard to its regulation by pro- and anti-apoptotic Bcl-2 family proteins such as Bid, Bax and Bcl-xL.