MoCox6 is a potential fungicide target regulating mitophagy in Magnaporthe oryzae

Mitophagy is a key mitochondrial quality-control pathway required for stress adaptation, but how damaged mitochondria are recognized and cleared in Magnaporthe oryzae remains poorly understood. In our recent study, we found that upon outer mitochondrial membrane disruption, inner mitochondrial membrane (IMM) protein MoCox6 is rendered available for engagement with cytosolic MoAtg5 and MoAtg14 to drive mitophagy, whereas MoSirt5-mediated desuccinylation of MoCox6 at Lys144 weakens these interactions and thereby restrains mitophagic flux. Further analyses identified Asp95 at the MoSirt5-MoCox6 interface as a pivotal residue coupling mitochondrial metabolic control to mitophagy. A high-throughput virtual screening targeting an Asp95-centered pocket in MoCox6 identified Pan-RAS-IN-1, a small molecule that effectively suppresses rice blast incidence and exhibits broad-spectrum antifungal activity. Collectively, these findings identify MoCox6 as an IMM regulator of mitophagy whose succinylation state links mitochondrial metabolic cues to mitochondrial turnover, while highlighting mitochondrial quality control as a potential target for fungal disease management.Abbreviations: ATG, autophagy related; IMM, inner mitochondrial membrane; OMM, outer mitochondrial membrane; MoCox6, Magnaporthe oryzae cytochrome c oxidase subunit 6; MoSirt5, Magnaporthe oryzae sirtuin 5 desuccinylase.