Mitochondrial Pathways in Apoptosis

描述(申请人提供)：我们早期的工作使用了各种基于细胞和体外的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膜，使其对大分子具有通透性。虽然这个非常简单的系统，使用定义的脂质体和重组的Bcl-2家族蛋白的混合物，已被证明在没有其他蛋白的情况下用于确定这些蛋白的功能，但在天然线粒体中的情况当然要复杂得多。在这里，我们描述了一些实验，这些实验旨在验证以下假设：1)蛋白水解酶对线粒体外膜通透性(MOMP)的调节，2)MOMP在缺乏活性caspase的情况下的细胞后果，以及3)在非洲爪哇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.