Tsujimoto Yoshihide
Osaka University Medical School, Graduate School of Medicine, CREST of Japanese Science and Technology, Suita.
Biosci Rep. 2002 Feb;22(1):47-58. doi: 10.1023/a:1016061006256.
An increase in the permeability of outer mitochondrial membrane is central to apoptotic cell death, and results in the release of several apoptogenic factors such as cytochrome c into the cytoplasm to activate downstream destructive programs. The voltage-dependent anion channel (VDAC or mitochondrial porin) plays an essential role in disrupting the mitochondrial membrane barrier and is regulated directly by members of the Bcl-2 family proteins. Anti-apoptotic Bcl-2 family members interact with and close the VDAC, whereas some, but not all, proapoptotic members interact with VDAC to open protein-conducting pore through which apoptogenic factors pass. Although the VDAC is involved directly in breaking the mitochondrial membrane barrier and is a known component of the permeability transition pore complex, VDAC-dependent increase in outer membrane permeability can be independent of the permeability transition event such as mitochondrial swelling followed by rupture of the outer mitochondrial membrane. VDAC interacts not only with Bcl-2 family members but also with proteins such as gelsolin, an actin regulatory protein, and appears to be a convergence point for a variety of cell survival and cell death signals.
线粒体外膜通透性增加是凋亡性细胞死亡的核心环节，会导致细胞色素c等多种凋亡诱导因子释放到细胞质中，从而激活下游的破坏程序。电压依赖性阴离子通道（VDAC或线粒体孔蛋白）在破坏线粒体膜屏障过程中发挥着重要作用，并且直接受Bcl-2家族蛋白成员的调控。抗凋亡的Bcl-2家族成员与VDAC相互作用并使其关闭，而一些（并非全部）促凋亡成员与VDAC相互作用，打开蛋白质传导孔，凋亡诱导因子可通过该孔道通过。尽管VDAC直接参与破坏线粒体膜屏障，并且是通透性转换孔复合体的已知组成部分，但依赖于VDAC的外膜通透性增加可能独立于通透性转换事件，如线粒体肿胀继而线粒体外膜破裂。VDAC不仅与Bcl-2家族成员相互作用，还与诸如凝溶胶蛋白（一种肌动蛋白调节蛋白）等蛋白质相互作用，并且似乎是各种细胞存活和细胞死亡信号的汇聚点。
