title: Both the p33 and p55 subunits of the Helicobacter pylori VacA toxin are targeted to mammalian mitochondria.
abstract: Helicobacter pylori infection causes peptic ulcers and gastric cancer. A major toxin secreted by H. pylori is the bipartite vacuolating cytotoxin A, VacA. The toxin is believed to enter host cells as two subunits: the p55 subunit (55 kDa) and the p33 subunit (33 kDa). At the biochemical level, it has been shown that VacA forms through the assembly of large multimeric pores composed of both the p33 subunit and the p55 subunit in biological membranes. One of the major target organelles of VacA is the mitochondria. Since only the p33 subunit has been reported to be translocated into mitochondria and the p55 subunit is not imported, it has been contentious as to whether VacA assembles into pores in a mitochondrial membrane. Here we show the p55 protein is imported into the mitochondria along with the p33 protein subunit. The p33 subunit integrally associates with the mitochondrial inner membrane, and both the p33 subunit and the p55 subunit are exposed to the mitochondrial intermembrane space. Their colocalization suggests that they could reassemble and form a pore in the inner mitochondrial membrane.
authors.affiliation: Host Pathogens Molecular Biology Unit, Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne 3800, Australia.
authors.forename: Jung Hock
authors.initials: JH
authors.lastname: Foo
authors.forename: Janetta G
authors.initials: JG
authors.lastname: Culvenor
authors.forename: Richard L
authors.initials: RL
authors.lastname: Ferrero
authors.forename: Terry
authors.initials: T
authors.lastname: Kwok
authors.forename: Trevor
authors.initials: T
authors.lastname: Lithgow
authors.forename: Kipros
authors.initials: K
authors.lastname: Gabriel
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; C074689:VacA protein, Helicobacter pylori