Targeting of the pro-apoptotic VDAC-like porin (PorB) of Neisseria gonorrhoeae to mitochondria of infected cells

Infection of cell cultures with Neisseria gonorrhoeae results in apoptosis that is mediated by the PorB porin. During the infection process porin tran slocates from the outer bacterial membrane into host cell membranes where i ts channel activity is regulated by nucleotide binding and voltage-dependen t gating, features that are shared by the mitochondrial voltage-dependent a nion channel (VDAC). Here we show that porin is selectively and efficiently transported to mitochondria of infected cells. Prevention of porin translo cation also blocked the induction of apoptosis. Mitochondria of cells treat ed with porin both in vitro and in vivo were depleted of cytochrome c and u nderwent permeability transition. Overexpression of Bcl-2 blocked porin-ind uced apoptosis. The release of cytochrome c occurred independently of activ e caspases but was completely prevented by Bcl-2. Our data suggest that the Neisseria porin can, like its eukaryotic homologue, function at the mitoch ondrial checkpoint to mediate apoptosis.