ERAD Component MoHrd3 Facilitates Pathogenicity and Establishes a Direct Regulation on Autophagy in <i>Magnaporthe Oryzae</i>

Both ER-associated degradation (ERAD) and autophagy play crucial roles in maintaining ER protein homeostasis. However, the regulatory relationship between ERAD and autophagy has remained unclear. Here, we report that MoHrd3 is an ERAD component that regulates autophagy in Magnaporthe oryzae, which causes devastating blast disease on rice and wheat. We found that MoHrd3 is important for growth, conidiation, appressorium formation, and expansion of infection hyphae. Further studies showed that the autophagy level is reduced with an impaired fusion between the autophagosome and the vacuole in the MoHrd3 deletion mutant. Interestingly, MoHrd3 directly interacts with MoAtg8, located on the autophagosome, and MoYpt7, situated on the vacuolar membrane. respectively. By serving as a mediator of the protein interaction between MoAtg8 and MoYpt7, MoHrd3 facilitates the fusion of these organelles. Further, we showed that the MoHrd3-dependent fusion between the autophagosome and the vacuole is crucial for pathogenicity. In addition, MoHrd3 also works as an adaptor protein to promote the autophagic degradation of a GPCR protein MoPth11, which is required for appressorium formation and pathogenicity. Our discovery of MoHrd3's role in autophagy establishes a direct connection between ERAD and autophagy, revealing the intricate mechanisms governing protein quality control in this devastating plant pathogen.