Mitophagy Increases Resistance against Infection of Pseudomonas aeruginosa through the PHB2 / PARL / PGAM5 / PINK1 Axis

Abstract Pseudomonas aeruginosa (P.a) is a common opportunistic pathogen causing serious infection and complications in diverse populations, especially under immunodeficient conditions. Previous studies indicate that mitophagy activation is related to multiple conditions and processes in the human body, including infectious diseases. It has been recently implicated that the PARL-PGAM5-PINK1 axis activates mitophagy, but its regulatory role in pneumonia is unclear. We hypothesize that mitophagy receptor PHB2 orchestrates an autophagic process through PARL and PGAM5 to limit P.a. infection and inflammation. By knocking down PHB2, we explored the regulatory role of mitophagy in P.a infection and evaluated the underlying mechanism of the PARL-PGAM5-PINK1 signals both in vitro and in P.a pneumonia mice. Our study also reveals that the critical factors, such as PARL and PINK1, may have potential for therapeutic targeting during Pseudomonas infection.