Antonsson B
Serono Pharmaceutical Research Institute, 14, chemin des Aulx, 1228 Plan-les-Ouates, Geneva, Switzerland.
Cell Tissue Res. 2001 Dec;306(3):347-61. doi: 10.1007/s00441-001-0472-0. Epub 2001 Oct 30.
Two major intracellular apoptosis signaling cascades have been characterized, the mitochondrial pathway and the death receptor pathway. The mitochondrial pathway is regulated by members of the Bcl-2 protein family. The members of this family can be subdivided into anti- and pro-apoptotic proteins. The pro-apoptotic members are further divided into two groups, the multidomain and the 'BH3 domain only' proteins. When cells are exposed to apoptotic stimulation, pro-apoptotic proteins are activated through post-translational modifications or changes in their conformation. The main site of action of the multidomain proteins are the mitochondria, where these proteins induce permeabilization of the outer membrane resulting in the release of proteins, including cytochrome c, from the intermembrane space. In the cytosol cytochrome c activates caspase cascades ultimately leading to cell death. Mounting evidence indicates that apoptosis is involved in a wide range of pathological conditions. Recent studies suggest that the mitochondrial signaling pathway is involved in several diseases. Although, so far, with the exception of C. elegans, most studies on apoptosis have been performed in mammalian systems, recently homologues to the Bcl-2 family members, including pro-apoptotic members, have been identified in Drosophila and zebrafish. Here the structure and function of the various pro-apoptotic Bcl-2 family members, their effects on mitochondria, and their involvement in diseases are discussed.
已鉴定出两种主要的细胞内凋亡信号级联反应，即线粒体途径和死亡受体途径。线粒体途径受Bcl-2蛋白家族成员调控。该家族成员可分为抗凋亡蛋白和促凋亡蛋白。促凋亡成员进一步分为两组，即多结构域蛋白和“仅含BH3结构域”蛋白。当细胞受到凋亡刺激时，促凋亡蛋白通过翻译后修饰或构象变化而被激活。多结构域蛋白的主要作用位点是线粒体，这些蛋白在该处诱导外膜通透性增加，导致包括细胞色素c在内的蛋白质从膜间隙释放。在细胞质中，细胞色素c激活半胱天冬酶级联反应，最终导致细胞死亡。越来越多的证据表明，凋亡涉及多种病理状况。最近的研究表明，线粒体信号通路与多种疾病有关。尽管到目前为止，除了秀丽隐杆线虫外，大多数关于凋亡的研究都是在哺乳动物系统中进行的，但最近在果蝇和斑马鱼中已鉴定出与Bcl-2家族成员（包括促凋亡成员）同源的蛋白。本文将讨论各种促凋亡Bcl-2家族成员的结构和功能、它们对线粒体的影响以及它们与疾病的关系。
