Dejean L M, Martinez-Caballero S, Kinnally K W
Department of Basic Sciences, College of Dentistry, New York University, NY 10010, USA.
Cell Death Differ. 2006 Aug;13(8):1387-95. doi: 10.1038/sj.cdd.4401949. Epub 2006 May 5.
Apoptosis is a phenomenon fundamental to higher eukaryotes and essential to mechanisms controlling tissue homeostasis. Bcl-2 family proteins tightly control this cell death program by regulating the permeabilization of the mitochondrial outer membrane and, hence, the release of cytochrome c and other proapoptotic factors. Mitochondrial apoptosis-induced channel (MAC) is the mitochondrial apoptosis-induced channel and is responsible for cytochrome c release early in apoptosis. MAC activity is detected by patch clamping mitochondria at the time of cytochrome c release. The Bcl-2 family proteins regulate apoptosis by controlling the formation of MAC. Depending on cell type and apoptotic inducer, Bax and/or Bak are structural component(s) of MAC. Overexpression of the antiapoptotic protein Bcl-2 eliminates MAC activity. The focus of this review is a biophysical characterization of MAC activity and its regulation by Bcl-2 family proteins, and ends with some discussion of therapeutic targets.
细胞凋亡是高等真核生物的一种基本现象，对于控制组织稳态的机制至关重要。Bcl-2家族蛋白通过调节线粒体外膜的通透性，从而控制细胞色素c和其他促凋亡因子的释放，紧密调控这一细胞死亡程序。线粒体凋亡诱导通道（MAC）是线粒体凋亡诱导通道，负责在凋亡早期释放细胞色素c。在细胞色素c释放时，通过膜片钳技术检测线粒体来测定MAC活性。Bcl-2家族蛋白通过控制MAC的形成来调节细胞凋亡。根据细胞类型和凋亡诱导剂的不同，Bax和/或Bak是MAC的结构成分。抗凋亡蛋白Bcl-2的过表达会消除MAC活性。本综述的重点是MAC活性的生物物理特性及其受Bcl-2家族蛋白的调控，并最后对治疗靶点进行了一些讨论。
