Structure-guided targeting of MoAtg8 reveals an autophagy-mediated detoxification pathway

Macroautophagy/autophagy is typically viewed as a route for removing cytosolic material to the vacuole or lysosome. However, interactions with the autophagy machinery may also determine the fate of small molecules. Structure-guided screening in Magnaporthe oryzae identified nordihydroguaiaretic acid (NDGA) as a high-affinity ligand of MoAtg8. NDGA inhibited early infection-related development and damaged fungal membranes, whereas MoAtg8-dependent autophagy promoted its vacuolar delivery and reduced its toxic effects on the fungus. These findings revealed a protective role of Atg8 for handling a toxic compound and suggested that weakening this buffering pathway could enhance antifungal activity.