Cadmium (Cd), a highly toxic element, poses significant constraints on global crop distribution and productivity. A better understanding of the molecular mechanisms underlying the response to Cd stress will help improve plant performance under Cd-exposed conditions. Here, we aimed to elucidate the complex response mechanisms of two oat varieties (CEav5651 and T1402) to Cd stress through integrated metabolomic and transcriptomic analyses. Our findings demonstrated that CEav5651 exhibited superior Cd tolerance compared to T1402. Metabolomic profiling revealed that glutathione and nicotianamine levels were significantly elevated in both varieties under Cd stress, with CEav5651 accumulating substantially higher concentrations of these two metabolites than T1402. This differential accumulation was corroborated by corresponding transcriptomic alterations. Critically, exogenous application of glutathione or nicotianamine markedly enhanced plant Cd tolerance. Heterologous overexpression of AsGS3 and AsNAS17, key genes in glutathione and nicotianamine biosynthesis, respectively, in tobacco (Nicotiana tabacum) elevated endogenous levels of these metabolites and conferred enhanced Cd tolerance. Our findings reveal the pivotal, coordinated role of glutathione and nicotianamine metabolism in Cd tolerance and provide promising genetic targets for breeding resilient crops.
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