Vibrio cholerae T3SS Effector VopE Modulates Mitochondrial Dynamics and Innate Immune Signaling by Targeting Miro GTPases

• V. cholerae T3SS effector VopE is targeted to mitochondria during infection
• VopE binds and activates GTP hydrolysis of Miro GTPases
• Miro promotes perinuclear mitochondrial clustering during infection, which VopE inhibits
• VopE modulation of mitochondrial dynamics inhibits host inflammatory responses

SummaryThe 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.

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