Ugarte-Uribe Begoña, García-Sáez Ana J
Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe Seyler Straße 4, 72076 Tübingen, Germany.
Biofisika Institute (UPV/EHU, CSIC), Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain.
Philos Trans R Soc Lond B Biol Sci. 2017 Aug 5;372(1726). doi: 10.1098/rstb.2016.0217.
The permeabilization of the mitochondrial outer membrane by Bax and Bak during apoptosis is considered a key step and a point of no return in the signalling pathway. It is always closely related to the reorganization of mitochondrial cristae that frees cytochrome to the intermembrane space and to massive mitochondrial fragmentation mediated by the dynamin-like protein Drp1. Despite multiple evidence in favour of a functional link between these processes, the molecular mechanisms that connect them and their relevance for efficient apoptosis signalling remain obscure. In this review, we discuss recent progress on our understanding of how Bax forms pores in the context of Drp1-stabilized signalling platforms at apoptotic foci in mitochondria.This article is part of the themed issue 'Membrane pores: from structure and assembly, to medicine and technology'.
在细胞凋亡过程中,Bax和Bak介导的线粒体外膜通透性改变被认为是信号通路中的关键步骤和不可逆转的节点。它总是与线粒体嵴的重组密切相关,线粒体嵴的重组使细胞色素c释放到膜间隙,并与由动力蛋白样蛋白Drp1介导的线粒体大量碎片化有关。尽管有多项证据支持这些过程之间存在功能联系,但连接它们的分子机制及其对有效细胞凋亡信号传导的相关性仍不清楚。在这篇综述中,我们讨论了最近在理解Bax如何在线粒体凋亡灶中由Drp1稳定的信号平台背景下形成孔方面取得的进展。本文是主题为“膜孔:从结构与组装到医学与技术”特刊的一部分。