Deubiquitinase MoAMSH inhibits autophagy by targeting MoAtg6 in Magnaporthe oryzae.

Ubiquitination is a highly conserved post-translational modification in eukaryotes, and the deubiquitinase associated molecule with the SH3 domain of STAM (AMSH) plays a critical role in reversing this modification, thereby regulating various cellular processes. However, the specific mechanisms by which AMSH influences pathogenicity through autophagy in pathogenic fungi remain poorly understood. In this study, we investigate the multifaceted role of MoAMSH in the development and pathogenicity of Magnaporthe oryzae. We identify MoAMSH and demonstrate that the E346 residue is crucial for its interactions with MoHse1, MoVps24, and MoAtg13. Functional analyses indicate that MoAMSH is essential for growth, conidiation, conidial germination, appressorium formation, and overall pathogenicity. Additionally, MoAMSH plays a significant role in the response to abiotic stress and exhibits K63-linked deubiquitination activity. Our findings further reveal that MoAMSH regulates development and pathogenicity by participating in MAPK pathways. Notably, MoAMSH acts as a negative regulator of autophagy by inhibiting the interaction between MoAtg6 and MoVps34 through the deubiquitination of K63-linked ubiquitinated MoAtg6. In summary, our results uncover a novel regulatory pathway related to autophagy in pathogenic fungi and suggest that AMSH may serve as a potential target for antifungal therapies.