Bacterial Porin Disrupts Mitochondrial Membrane Potential and Sensitizes Host Cells to Apoptosis
Autor(en): | Kozjak-Pavlovic, Vera Dian-Lothrop, Elke A. Meinecke, Michael Kepp, Oliver Ross, Katharina Rajalingam, Krishnaraj Harsman, Anke Hauf, Eva Brinkmann, Volker Guenther, Dirk Herrmann, Ines Hurwitz, Robert Rassow, Joachim Wagner, Richard Rudel, Thomas |
Stichwörter: | ASSEMBLY MACHINERY; BETA-BARREL PROTEINS; BIOGENESIS; CYTOCHROME-C RELEASE; EPITHELIAL-CELLS; IMPORT PORE; INNER MEMBRANE; Microbiology; NEISSERIA-GONORRHOEAE; OUTER-MEMBRANE; Parasitology; PROTECTS CELLS; Virology | Erscheinungsdatum: | 2009 | Herausgeber: | PUBLIC LIBRARY SCIENCE | Journal: | PLOS PATHOGENS | Volumen: | 5 | Ausgabe: | 10 | Zusammenfassung: | 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. |
ISSN: | 15537366 | DOI: | 10.1371/journal.ppat.1000629 |
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geprüft am 02.05.2024