MoSec13 combined with MoGcn5b modulates MoAtg8 acetylation and regulates autophagy in .

Macroautophagy/autophagy is an evolutionarily conserved cellular degradation process that is crucial for cellular homeostasis in . However, the precise regulatory mechanisms governing autophagy in this organism remain unclear. In this study, we found a multiregional localization of MoSec13 to the vesicle membrane, endoplasmic reticulum, nucleus, and perinucleus. MoSec13 negatively regulated autophagy through specific amino acid residues in its own WD40 structural domain by interacting with MoAtg7 and MoAtg8. We also found that the histone acetyltransferase MoGcn5b mediated the acetylation of MoAtg8 and regulated autophagy activity. Subsequently, we further determined that MoSec13 regulated the acetylation status of MoAtg8 by controlling the interaction between MoGcn5b and MoAtg8 in the nucleus. In addition, MoSec13 maintained lipid homeostasis by controlling TORC2 activity. This multilayered integration establishes MoSec13 as an essential node within the autophagic regulatory network. Our findings fill a critical gap in understanding the role of Sec13 in autophagy of filamentous fungi and provide a molecular foundation for developing new therapeutic strategies against rice blast fungus. BFA: brefeldin A; BiFC: bimolecular fluorescence complementation; CM: complete medium; CMAC: 7-amino-4-chloromethylcoumarin; Co-IP: co-immunoprecipitation; COPII: coat complex II; GFP: green fluorescent protein; HPH: hygromycin phosphotransferase; MM-N: nitrogen-starvation conditions; NPC: nuclear pore complex; PAS: phagophore assembly site; PE: phosphatidylethanolamine; UPR: unfolded protein response.