Mitochondrial Pathways in Apoptosis

描述（由申请人提供）：我们早期的工作已经使用了各种基于细胞的体外系统来探索线粒体在细胞凋亡中的作用。特别是，以前的研究表明，Bcl-2家族蛋白可以直接作用于脂质体膜，使其对大分子具有渗透性。然而，这个非常简单的系统，使用确定的脂质体和重组Bcl-2家族蛋白的混合物，已被证明是有用的，在没有其他蛋白的情况下，这些蛋白的功能，在天然的peption的情况当然是复杂得多。在这里，我们描述了实验设计来测试假设1）蛋白酶调节线粒体外膜透化（MOMP），2）细胞的MOMP的后果在没有活性半胱天冬酶，和3）在体内的线粒体凋亡途径的调节，在非洲爪蟾的发展。

DESCRIPTION (provided by applicant): Our earlier work has used a variety of cell-based and in vitro systems to explore the role of mitochondria in apoptosis. In particular, previous studies have shown that Bcl-2-family proteins can act directly on liposomal membranes to make them permeable to large macromolecules. Whereas this very simple system, using defined liposomes and mixtures of recombinant Bcl-2-family proteins has proven to be useful for defining the functions of these proteins in the absence of other proteins, the situation in the native mitochondrion is of course much more complex. Here we describe experiments designed to test hypotheses concerning 1) protease regulation of mitochondrial outer membrane permeabilization (MOMP), 2) cellular consequences of MOMP in the absence of active caspases, and 3) the regulation of mitochondrial apoptosis pathways in vivo, in Xenopus development.