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SummaryIron is an essential micronutrient for plant growth and development. Under low iron conditions, Arabidopsis plants take up soil iron using the root iron transporter IRT1. In addition to iron, IRT1 also transports others divalent metals including cadmium that consequently accumulates into plant tissues and enters the food chain. IRT1 expression was shown to be regulated at the transcriptional and post-translational levels by its essential metal substrates to maximize iron uptake while limiting the accumulation of zinc, manganese or cobalt. Here, we characterized the regulation of IRT1 by cadmium and uncovered a cadmium-mediated downregulation of IRT1 protein by endocytosis. A short term exposure to cadmium indeed decreased the celle surface levels of IRT1 through endocytosis and degradation. This is mediated through the direct binding of cadmium to histidine residues within the regulatory loop of IRT1. Moreover, we demonstrated that cadmium-induced IRT1 degradation uses ubiquitin-mediated endocytosis driven by the IDF1 E3 ligase. Altogether, this work sheds light on the mechanisms of cadmium-mediated downregulation of IRT1 and offers a unique opportunity to boost plant cadmium uptake in phytoremediation/phytoextraction strategies.