La Jolla Institute, La Jolla, California, 92037.
J Cell Biochem. 2014 Apr;115(4):632-40. doi: 10.1002/jcb.24709.
Mitochondria play a critical role in apoptosis, or programmed cell death, by releasing apoptogenic factors from the intermembrane space. This process, known as mitochondrial outer membrane permeabilization (MOMP), is tightly regulated by the Bcl-2 family proteins. Pro-apoptotic Bcl-2 family members, Bax and Bak, change their conformation when activated by BH3 domain-only proteins in the family and permeabilize the MOM, whereas pro-survival members inhibit permeabilization. The precise nature of the apoptotic pore in the MOM is unknown, but is probably lipidic. Furthermore, it has been realized that there is another layer of MOMP regulation by a protein factor termed the catalyst in the MOM in order for Bax/Bak to achieve efficient and complete membrane permeabilization. Mitochondrial dynamics do not affect MOMP directly, but seem closely coordinated with MOMP for swift protein efflux from mitochondria. This review will present current views on the molecular mechanisms and regulation of MOMP and conclude with recent developments in clinical applications based on the knowledge gleaned from the investigation.
线粒体在细胞凋亡（程序性细胞死亡）中起着至关重要的作用，通过从膜间空间释放促凋亡因子。这个过程被称为线粒体外膜通透性（MOMP），由 Bcl-2 家族蛋白严格调控。促凋亡 Bcl-2 家族成员 Bax 和 Bak 在被家族中的 BH3 结构域蛋白激活时会改变构象，并使 MOM 通透性增加，而促生存成员则抑制通透性。MOM 中凋亡孔的确切性质尚不清楚，但可能是脂性的。此外，人们已经意识到，为了使 Bax/Bak 实现有效的完全膜通透性，MOMP 的调节还有另一层，由一种称为 MOM 中的催化剂的蛋白因子来实现。线粒体动力学不会直接影响 MOMP，但似乎与 MOMP 密切协调，以便快速从线粒体中排出蛋白质。这篇综述将介绍 MOMP 的分子机制和调控的最新观点，并以从研究中获得的知识为基础，总结最近在临床应用方面的进展。
