Parkin-mediated responses against infection and wound involve TSPO-VDAC complex in Drosophila

• Parkin mediates infection and wound responses in Drosophila.
• Mitochondrial TSPO-VDAC complex participates in parkin-mediated immune response.
• Parkin may function upstream of TSPO-VDAC complex to mediate immune response.

Parkin, an E3 ubuquitin ligase associated with Parkinson's disease (PD), has recently been implicated in mediating innate immunity. However, molecular details regarding parkin-mediated immune response remain to be elucidated. Here, we identified mitochondrial TSPO-VDAC complex to genetically interact with parkin in mediating responses against infection and wound in Drosophila. The loss-of-function mutation in parkin results in defective immune response against bacterial infection. Additionally, parkin mutant larvae showed hypersensitivity against wound regardless of bacterial infection. Interestingly, the combinatorial trans-heterozygotic mutations in parkin and TSPO, or parkin and VDAC showed similar lethal tendency with parkin homozygous mutants. Furthermore, knockdown of TSPO alone also resulted in defective responses to infection and wound analogously to parkin mutants. Taken together, we propose that parkin cooperates with TSPO-VDAC complex to mediate responses against infection and wound.