title: Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial fission machinery to induce host cell death.
abstract: A number of pathogenic bacteria target mitochondria to modulate the host's apoptotic machinery. Studies here revealed that infection with the human gastric pathogen Helicobacter pylori disrupts the morphological dynamics of mitochondria as a mechanism to induce host cell death. The vacuolating cytotoxin A (VacA) is both essential and sufficient for inducing mitochondrial network fragmentation through the mitochondrial recruitment and activation of dynamin-related protein 1 (Drp1), which is a critical regulator of mitochondrial fission within cells. Inhibition of Drp1-induced mitochondrial fission within VacA-intoxicated cells inhibited the activation of the proapoptotic Bcl-2-associated X (Bax) protein, permeabilization of the mitochondrial outer membrane, and cell death. Our data reveal a heretofore unrecognized strategy by which a pathogenic microbe engages the host's apoptotic machinery.
authors: Department of Microbiology and Institute for Genomic Biology, University of Illinois, Urbana, IL 61801, USA.
authors: Prashant
authors: P
authors: Jain
authors: Zhao-Qing
authors: ZQ
authors: Luo
authors: Steven R
authors: SR
authors: Blanke
mesh_terms: D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D034281:Dynamins; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D005434:Flow Cytometry; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000382:microbiology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C074689:VacA protein, Helicobacter pylori; D051028:bcl-2-Associated X Protein; D049452:Green Fluorescent Proteins; D045304:Cytochromes c; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins