Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing 
The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection.
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Metadaten
Author:Vera Kozjak-Pavlovic, Elke A. Dian-Lothrop, Michael Meinecke, Oliver Kepp, Katharina Ross, Krishnaraj Rajalingam, Anke Harsman, Eva Hauf, Volker Brinkmann, Dirk Günther, Ines Herrmann, Robert Hurwitz, Joachim Rassow, Richard Wagner, Thomas Rudel
URN:urn:nbn:de:hebis:30-105273
DOI:http://dx.doi.org/10.1371/journal.ppat.1000629
ISSN:1553-7374
Parent Title (English):PLoS pathogens
Document Type:Article
Language:English
Date of Publication (online):2011/09/09
Year of first Publication:2009
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2011/09/09
Note:
Copyright: © 2009 Kozjak-Pavlovic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source:PLoS Pathogens 5(10): e1000629. doi: 10.1371/journal.ppat.1000629
HeBIS PPN:274584344
Institutes:Biochemie und Chemie
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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