FIG. 6.

Model of the regulation of urethral epithelial programmed cell death after infection with N. gonorrhoeae. (A) Infection of UECs with N. gonorrhoeae or treatment with purified gonococcal PorB IB activates NF-κB and increases the expression of antiapoptotic factors that can function to regulate apoptosis initiated by either the extrinsic or intrinsic death pathway. Infection with the gonococcus does not alter the expression status of key proapoptotic members of the Bcl-2 family. IAP, inhibition of apoptosis; AIF, apoptosis-inducing factor. (B) The increased expression of antiapoptotic factors (e.g., Bfl-1) by gonococcal porin (pIB) may prevent the opening of a Bax-mediated VDAC pore, sequestering cyt c in the intermitochondrial membrane space (IMMS). (C) In the absence of key antiapoptotic regulators, proapoptotic Bcl-2 family members (i.e., Bax) may interact with and promote the open conformation of gonococcal pIB, allowing for the release of cyt c. Increased levels of antiapoptotic factors (i.e., Bfl-1) may maintain pIB in a closed conformation either by interacting directly with pIB or by preventing its association with Bax or other proapoptotic factors. OMM and IMM, outer and inner mitochondrial membranes, respectively. (D) Gonococcal pIB may translocate to the outer mitochondrial membrane (OMM) of UECs and interact directly with VDAC, preventing the release of cyt c through an otherwise open VDAC pore. It is also possible, but unlikely, that Bfl-1 may interact directly with VDAC to influence the size of the VDAC channel.