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 breakdown of the mitochondrial membrane potential (DeltaPsi(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 DeltaPsi(m). The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce DeltaPsi(m) loss and apoptosis, demonstrating that dissipation of DeltaPsi(m) is a requirement for cell death caused by neisserial infection.
Kozjak-Pavlovic
Vera
V
Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
Dian-Lothrop
Elke A
EA
Meinecke
Michael
M
Kepp
Oliver
O
Ross
Katharina
K
Rajalingam
Krishnaraj
K
Harsman
Anke
A
Hauf
Eva
E
Brinkmann
Volker
V
Günther
Dirk
D
Herrmann
Ines
I
Hurwitz
Robert
R
Rassow
Joachim
J
Wagner
Richard
R
Rudel
Thomas
T
D017209:Apoptosis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008954:Models, Biological; D009344:Neisseria gonorrhoeae / Q000737:chemistry / Q000472:pathogenicity / Q000502:physiology; D016870:Neisseriaceae Infections / Q000378:metabolism / Q000473:pathology; D018272:Porins / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology
D001426:Bacterial Proteins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D018272:Porins; C057699:porin protein, Neisseria; D045304:Cytochromes c; D020169:Caspases