Mitochondrial dysfunction in cell death.

细胞死亡中的线粒体功能障碍。

• 批准号: 6764193
• 负责人: DONALD DAVID NEWMEYER
• 金额: $ 30.08万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6764193
• 关键词: BCL2 gene /protein; Xenopus oocyte; affinity chromatography; alternatives to animals in research; apoptosis; cell cycle; cell free system; cysteine endopeptidases; cytochrome c; enzyme activity; mitochondrial disease /disorder; mitochondrial membrane; molecular cloning; protease inhibitor; protein degradation; protooncogene

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.

描述（由申请人提供）：线粒体在 细胞凋亡（程序性细胞死亡）。特别是蛋白质的释放，例如 作为细胞色素 c 和 Smac/DIABLO 从线粒体膜间隙进入 胞质溶胶是 caspase 激活的重要触发因素，进而导致 细胞凋亡的特征事件。在这里我们提出研究探索 该凋亡途径涉及线粒体的各个方面。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 激活。其次，我们研究线粒体的变化。 外膜透化作用产生的功能；在某种情况下 当半胱天冬酶被抑制时，这些线粒体效应可能是原因 为了细胞的死亡。最后，我们探索外在的本质 线粒体膜透化事件，特别是其 促凋亡和抗凋亡 Bcl-2 家族蛋白（例如 Bid、Bax）的调节 和Bcl-xL。