Müller A, Günther D, Brinkmann V, Hurwitz R, Meyer T F, Rudel T
Max Planck Institute for Infection Biology, Department of Molecular Biology and Central Support Unit, Schumannstrasse 21-22, 10117 Berlin, Germany.
EMBO J. 2000 Oct 16;19(20):5332-43. doi: 10.1093/emboj/19.20.5332.
Infection of cell cultures with Neisseria gonorrhoeae results in apoptosis that is mediated by the PorB porin. During the infection process porin translocates from the outer bacterial membrane into host cell membranes where its channel activity is regulated by nucleotide binding and voltage-dependent gating, features that are shared by the mitochondrial voltage-dependent anion channel (VDAC). Here we show that porin is selectively and efficiently transported to mitochondria of infected cells. Prevention of porin translocation also blocked the induction of apoptosis. Mitochondria of cells treated with porin both in vitro and in vivo were depleted of cytochrome c and underwent permeability transition. Overexpression of Bcl-2 blocked porin-induced apoptosis. The release of cytochrome c occurred independently of active caspases but was completely prevented by Bcl-2. Our data suggest that the Neisseria porin can, like its eukaryotic homologue, function at the mitochondrial checkpoint to mediate apoptosis.
用淋病奈瑟菌感染细胞培养物会导致由PorB孔蛋白介导的细胞凋亡。在感染过程中，孔蛋白从细菌外膜转运到宿主细胞膜，其通道活性受核苷酸结合和电压依赖性门控调节，这些特性与线粒体电压依赖性阴离子通道（VDAC）相同。在此我们表明，孔蛋白被选择性且高效地转运到被感染细胞的线粒体中。阻止孔蛋白转运也会阻断细胞凋亡的诱导。在体外和体内用孔蛋白处理的细胞线粒体中，细胞色素c耗竭并发生通透性转换。Bcl-2的过表达可阻断孔蛋白诱导的细胞凋亡。细胞色素c的释放独立于活性半胱天冬酶发生，但被Bcl-2完全阻止。我们的数据表明，淋病奈瑟菌孔蛋白与其真核同源物一样，可在线粒体检查点发挥作用以介导细胞凋亡。
