Bacterial CipB is an exogenous receptor to drive the mitophagy-TFEB axis and promote pathogenesis.

Abstract

Mitophagy transports mitochondria to lysosomes for degradation to maintain energy homeostasis, inflammation, and immunity. Here, we identify CipB, a type III secretion system (T3SS) effector from Chromobacterium violaceum, as a novel exogenous mitophagy receptor. CipB targets mitochondria by the mitochondrial protein TUFM and recruits autophagosomes via its LC3-interacting region (LIR) motifs. This process initiates the mitophagy-TFEB axis, triggering TFEB nuclear translocation and suppression of proinflammatory cytokines, thereby promoting bacterial survival and pathogenesis. CipB represents a conserved family of T3SS effectors employed by diverse pathogens to manipulate host mitophagy. Using a mouse model, CipB's mitophagy receptor function is critical for C. violaceum colonization in the liver and spleen, underscoring its role in bacterial virulence. This study reveals a novel mechanism by which bacterial pathogens exploit host mitophagy to suppress immune responses, defining CipB as a paradigm for exogenous mitophagy receptors. These findings advance our understanding of pathogen-host interactions and highlight the mitophagy-TFEB axis as a potential signaling pathway against bacterial infection.