Natural Variation at the <em>FRD3</em> MATE Transporter Locus Reveals Cross-Talk between Fe Homeostasis and Zn Tolerance in <em>Arabidopsis thaliana</em>

<div><p>Zinc (Zn) is essential for the optimal growth of plants but is toxic if present in excess, so Zn homeostasis needs to be finely tuned. Understanding Zn homeostasis mechanisms in plants will help in the development of innovative approaches for the phytoremediation of Zn-contaminated sites. In this study, Zn tolerance quantitative trait loci (QTL) were identified by analyzing differences in the Bay-0 and Shahdara accessions of <em>Arabidopsis thaliana</em>. Fine-scale mapping showed that a variant of the Fe homeostasis-related <em>FERRIC REDUCTASE DEFECTIVE3</em> (<em>FRD3</em>) gene, which encodes a multidrug and toxin efflux (MATE) transporter, is responsible for reduced Zn tolerance in <em>A. thaliana</em>. Allelic variation in <em>FRD3</em> revealed which amino acids are necessary for FRD3 function. In addition, the results of allele-specific expression assays in F1 individuals provide evidence for the existence of at least one putative metal-responsive <em>cis</em>-regulatory element. Our results suggest that FRD3 works as a multimer and is involved in loading Zn into xylem. Cross-homeostasis between Fe and Zn therefore appears to be important for Zn tolerance in <em>A. thaliana</em> with FRD3 acting as an essential regulator.</p>