Abstract
Infection of cell cultures with Neisseria gonorrhoeae results in apoptosis that is mediated by the PorB porin. During the infection process porin translocates from the outer bacterial membrane into host cell membranes where its channel activity is regulated by nucleotide binding and voltage-dependent gating, features that are shared by the mitochondrial voltage-dependent anion channel (VDAC). Here we show that porin is selectively and efficiently transported to mitochondria of infected cells. Prevention of porin translocation also blocked the induction of apoptosis. Mitochondria of cells treated with porin both in vitro and in vivo were depleted of cytochrome c and underwent permeability transition. Overexpression of Bcl-2 blocked porin-induced apoptosis. The release of cytochrome c occurred independently of active caspases but was completely prevented by Bcl-2. Our data suggest that the Neisseria porin can, like its eukaryotic homologue, function at the mitochondrial checkpoint to mediate apoptosis.
MeSH terms
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Apoptosis* / drug effects
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Bacterial Outer Membrane Proteins / antagonists & inhibitors
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Bacterial Outer Membrane Proteins / metabolism*
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Bacterial Outer Membrane Proteins / pharmacology
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Caspase Inhibitors
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Caspases / metabolism
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Cell Membrane Permeability / drug effects
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Cytochrome c Group / metabolism
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Enzyme Activation / drug effects
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HeLa Cells
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Humans
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Immunohistochemistry
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Ion Channel Gating
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Jurkat Cells
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Mitochondria / drug effects
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Mitochondria / enzymology
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Mitochondria / metabolism*
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Mitochondria / microbiology*
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Mitochondrial Swelling / drug effects
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Neisseria gonorrhoeae / metabolism*
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Neisseria gonorrhoeae / pathogenicity
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Porins / antagonists & inhibitors
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Porins / metabolism*
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Porins / pharmacology
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Protein Transport / drug effects
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Voltage-Dependent Anion Channels
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bcl-X Protein
Substances
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BCL2L1 protein, human
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Bacterial Outer Membrane Proteins
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Caspase Inhibitors
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Cytochrome c Group
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Porins
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Proto-Oncogene Proteins c-bcl-2
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Voltage-Dependent Anion Channels
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bcl-X Protein
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porin protein, Neisseria
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Caspases