Department of Cell Biology, University of Geneva, 1211 Geneva 4, Switzerland.
Cold Spring Harb Perspect Biol. 2013 Jan 1;5(1):a011106. doi: 10.1101/cshperspect.a011106.
Although mitochondria are usually considered as supporters of life, they are also involved in cellular death. Mitochondrial outer membrane permeabilization (MOMP) is a crucial event during apoptosis because it causes the release of proapoptotic factors from the mitochondrial intermembrane space to the cytosol. MOMP is mainly controlled by the Bcl-2 family of proteins, which consists of both proapoptotic and antiapoptotic members. We discuss the current understanding of how activating and inhibitory interactions within this family lead to the activation and oligomerization of MOMP effectors Bax and Bak, which result in membrane permeabilization. The order of events leading to MOMP is then highlighted step by step, emphasizing recent discoveries regarding the formation of Bax/Bak pores on the outer mitochondrial membrane. Besides the Bcl-2 proteins, the mitochondrial organelle contributes to and possibly regulates MOMP, because mitochondrial resident proteins and membrane lipids are prominently involved in the process.
虽然线粒体通常被认为是生命的支持者，但它们也参与细胞死亡。线粒体膜通透性的改变（MOMP）是细胞凋亡过程中的一个关键事件，因为它导致促凋亡因子从线粒体膜间空间释放到细胞质中。MOMP 主要由 Bcl-2 蛋白家族控制，该家族由促凋亡和抗凋亡成员组成。我们讨论了目前对于这个家族内部的激活和抑制相互作用如何导致 MOMP 效应因子 Bax 和 Bak 的激活和寡聚化的理解，这导致了膜通透性的改变。然后，我们逐步强调导致 MOMP 的事件顺序，强调关于 Bax/Bak 孔在外层线粒体膜上形成的最新发现。除了 Bcl-2 蛋白，线粒体细胞器也有助于并可能调节 MOMP，因为线粒体驻留蛋白和膜脂质在这个过程中显著参与。
