Mitochondrial Pathways in Apoptosis

描述（由申请人提供）：我们早期的工作已经使用各种基于细胞和体外系统来探索线粒体在细胞凋亡中的作用。特别是，先前的研究表明，bcl -2家族蛋白可以直接作用于脂质体膜，使其能够渗透到大分子中。然而，这个非常简单的系统，使用确定的脂质体和重组bcl -2家族蛋白质的混合物，已被证明可用于确定这些蛋白质在缺乏其他蛋白质的情况下的功能，天然线粒体的情况当然要复杂得多。在这里，我们描述了旨在验证以下假设的实验：1)蛋白酶调节线粒体外膜通透性（MOMP）， 2)缺乏活性半胱天冬酶时MOMP的细胞后果，以及3)在爪蟾发育过程中体内线粒体凋亡途径的调节。

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.