Mitochondrial protein FgDML1 regulates DON toxin biosynthesis and cyazofamid sensitivity in Fusarium graminearum by affecting mitochondrial homeostasis

Fusarium graminearumis a global pathogen responsible for Fusarium head blight (FHB) in wheat, causing substantial yield losses and producing the mycotoxin deoxynivalenol (DON), which poses a threat to both human and animal health.Drosophila melanogasterMisato-Like protein (DML1) plays a critical role in regulating mitochondrial function, yet its function in filamentous fungi remains unexplored. In this study, we characterized FgDML1 inF. graminearum. FgDML1 interacts with the mitochondrial fission and fusion protein FgDnm1 to maintain mitochondrial stability, thereby positively regulating acetyl-CoA levels and ATP synthesis, which influences toxisome formation and ultimately affects DON toxin biosynthesis. Additionally, FgDML1 is involved in the regulation of toxin biosynthetic enzyme expression. In the ΔFgDML1 mutant, Complex III enzyme activity decreased, overexpression of complex III assembly factorsFgQCR2,FgQCR8, andFgQCR9may induce conformational changes in the Qi-site protein, specifically altering the sensitivity ofF. graminearumto respiratory inhibitor cyazofamid not Qo-site inhibitor pyraclostrobin and other fungicides. Furthermore, the loss of FgDML1 leads to defects in nutrient utilization, as well as in asexual and sexual reproduction, and pathogenicity. In conclusion, this study identifies a novel regulatory role for FgDML1 in DON toxin biosynthesis and cyazofamid sensitivity inF. graminearum. Our study provides a theoretical framework for understanding DON biosynthesis regulation inF. graminearumand identifies potential molecular targets for FHB control.