Nandi Ipsita, Aroeti Lior, Ramachandran Rachana Pattani, Kassa Ephrem G, Zlotkin-Rivkin Efrat, Aroeti Benjamin
Department of Cell and Developmental Biology, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem, Israel.
Cell Microbiol. 2021 Sep;23(9):e13352. doi: 10.1111/cmi.13352. Epub 2021 Jun 8.
A type III secretion system (T3SS) is used by Gram-negative bacterial pathogens to secrete and translocate a battery of proteins, termed effectors, from the bacteria directly into the host cells. These effectors, which are thought to play a key role in bacterial virulence, hijack and modify the activity of diverse host cell organelles, including mitochondria. Mitochondria-the energy powerhouse of the cell-are important cell organelles that play role in numerous critical cellular processes, including the initiation of apoptosis and the induction of innate immunity. Therefore, it is not surprising that pathogenic bacteria use mitochondrially targeted effectors to control host cell death and immunity pathways. Surprisingly, however, we found that despite their importance, only a limited number of type III secreted effectors have been characterised to target host mitochondria, and the mechanisms underlying their mitochondrial activity have not been sufficiently analysed. These include effectors secreted by the enteric attaching and effacing (A/E), Salmonella and Shigella bacterial pathogens. Here we give an overview of key findings, present gaps in knowledge and hypotheses concerning the mode by which these type III secreted effectors control the host and the bacterial cell life (and death) through targeting mitochondria.
III型分泌系统（T3SS）被革兰氏阴性细菌病原体用于分泌一系列蛋白质（称为效应蛋白），并将其从细菌直接转运到宿主细胞中。这些效应蛋白被认为在细菌毒力中起关键作用，它们劫持并改变包括线粒体在内的多种宿主细胞器的活性。线粒体——细胞的能量动力源——是重要的细胞器，在众多关键的细胞过程中发挥作用，包括凋亡的启动和先天免疫的诱导。因此，致病细菌利用靶向线粒体的效应蛋白来控制宿主细胞死亡和免疫途径也就不足为奇了。然而，令人惊讶的是，尽管线粒体很重要，但只有少数III型分泌效应蛋白被鉴定为靶向宿主线粒体，而且它们的线粒体活性背后的机制尚未得到充分分析。这些效应蛋白包括由肠道黏附性和脱屑性（A/E）细菌病原体、沙门氏菌和志贺氏菌分泌的效应蛋白。在此，我们概述了关键发现，指出了知识空白以及关于这些III型分泌效应蛋白通过靶向线粒体来控制宿主和细菌细胞生命（及死亡）方式的假设。
