GenX triggers concentration-dependent photosynthetic inhibition and defense strategy shifts in wheat (Triticum aestivum L.) seedlings

Hexafluoropropylene oxide dimer acid (GenX), a widely used alternative to perfluorooctanoic acid, has been increasingly detected in agricultural soils. However, its phytotoxic mechanisms at environmentally relevant concentrations remain poorly understood. In this study, the phytotoxicity of GenX at environmentally realistic concentrations (0.1–100 ng g −1 ) in wheat seedlings was systematically investigated using physiological and multi-omics (proteomic and metabolomic) analyses. GenX exposure led to insufficient activation of superoxide dismutase, resulting in persistent superoxide anion accumulation and specific oxidative stress that ultimately impaired photosynthetic efficiency and osmoregulatory capacity. In response, an antioxidant defense network involving peroxidase, glutathione, and proline was activated. Multi-omics analyses revealed that GenX-induced remodeling of amino acid metabolism enhanced reactive oxygen species scavenging and nitrogen homeostasis. Molecular evidence indicated that GenX caused concentration-dependent cellular damage and stress responses. As exposure levels increased, damage to the photosynthetic system progressed from functional impairment to structural disruption: at 0.1 ng g −1 , GenX primarily reduced light-harvesting efficiency by suppressing chlorophyll biosynthesis and destabilizing photosystem II, whereas higher levels caused structural damage to the photosynthetic apparatus and inhibited electron transport, thereby hindering carbon fixation. Defense mechanisms also shifted from protein translation to epigenetic regulation with increasing GenX concentration. This study provides the first comprehensive elucidation of the toxicity pathway of GenX in wheat at environmentally relevant concentrations, offering crucial mechanistic insights for ecological risk assessment and advancing understanding of the phytotoxicity of emerging substitute pollutants. • Phytotoxicity of GenX on wheat seedlings was uncovered from physiological, biochemical, protein, and metabolite levels. • GenX causes insufficient SOD activation and consequent persistent .•O 2 − accumulation. • Wheat regulates and reprograms amino acid metabolism to remove ROS and boost tolerance to GenX stress. • Molecular pathways linking chlorophyll synthesis inhibition to carbon fixation impairment were established.