Institute for Genetics, CECAD Research Center, University of Cologne, Cologne, Germany.
Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Cell Mol Life Sci. 2021 Apr;78(8):3777-3790. doi: 10.1007/s00018-021-03771-4. Epub 2021 Feb 12.
Apoptotic cell death is essential for development, immune function or tissue homeostasis, and its mis-regulation is linked to various diseases. Mitochondrial outer membrane permeabilization (MOMP) is a central event in the intrinsic apoptotic pathway and essential to control the execution of cell death. Here we review current concepts in regulation of MOMP focusing on the interaction network of the Bcl-2 family proteins as well as further regulatory elements influencing MOMP. As MOMP is a complex spatially and temporally controlled process, we point out the importance of single-molecule techniques to unveil processes which would be masked by ensemble measurements. We report key single-molecule studies applied to decipher the composition, assembly mechanism and structure of protein complexes involved in MOMP regulation.
细胞凋亡是细胞程序性死亡的一种形式，对于组织稳态和器官发生是必需的。细胞凋亡的失调与多种疾病有关。线粒体膜通透性的改变（MOMP）是细胞凋亡内在途径的一个核心事件，对于控制细胞死亡的执行是必不可少的。在这里，我们综述了 MOMP 调节的当前概念，重点介绍了 Bcl-2 家族蛋白相互作用网络以及影响 MOMP 的其他调节因子。由于 MOMP 是一个复杂的、受时空控制的过程，我们指出了单分子技术的重要性，它可以揭示被整体测量所掩盖的过程。我们报告了关键的单分子研究，用于破译参与 MOMP 调节的蛋白质复合物的组成、组装机制和结构。
