title: Vibrio cholerae T3SS effector VopE modulates mitochondrial dynamics and innate immune signaling by targeting Miro GTPases.
abstract: The cellular surveillance-activated detoxification and defenses (cSADD) theory postulates the presence of host surveillance mechanisms that monitor the integrity of common cellular processes and components targeted by pathogen effectors. Being organelles essential for multiple cellular processes, including innate immune responses, mitochondria represent an attractive target for pathogens. We describe a Vibrio cholerae Type 3 secretion system effector VopE that localizes to mitochondria during infection and acts as a specific GTPase-activating protein to interfere with the function of mitochondrial Rho GTPases Miro1 and Miro2. Miro GTPases modulate mitochondrial dynamics and interfering with this functionality effectively blocks innate immune responses that presumably require mitochondria as signaling platforms. Our data indicate that interference with mitochondrial dynamics may be an unappreciated strategy that pathogens use to block host innate immune responses that would otherwise control these bacterial infections. VopE might represent a bacterial effector that targets the cSADD surveillance response.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Masato
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Danilchanka
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: jmekalanos@hms.harvard.edu.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mekalanos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D016466:CHO Cells; D003412:Cricetulus; D003470:Culture Media; D020690:GTPase-Activating Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D014734:Vibrio cholerae / Q000276:immunology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D003470:Culture Media; D020690:GTPase-Activating Proteins; D016328:NF-kappa B; D020741:rho GTP-Binding Proteins