The oligopeptide transporter (OPT) family contains nine members in Arabidopsis. While there is some evidence that AtOPTs mediate the uptake of tetra-and pentapeptides, OPT homologs in rice (Oryza sativa; OsGT1) and Indian mustard (Brassica juncea; BjGT1) have been described as transporters of glutathione derivatives. This study investigates the possibility that two members of the AtOPT family, AtOPT6 and AtOPT7, may also transport glutathione and its conjugates. Complementation of the hgt1met1 yeast double mutant by plant homologs of the yeast glutathione transporter HGT1 (AtOPT6, AtOPT7, OsGT1, BjGT1) did not restore the growth phenotype, unlike complementation by HGT1. By contrast, complementation by AtOPT6 restored growth of the hgt1 yeast mutant on a medium containing reduced (GSH) or oxidized glutathione as the sole sulfur source and induced uptake of [ 3 H]GSH, whereas complementation by AtOPT7 did not. In these conditions, AtOPT6-dependent GSH uptake in yeast was mediated by a high affinity (K m 5 400 mM) and a low affinity (K m 5 5 mM) phase. It was strongly competed for by an excess oxidized glutathione and glutathione-N-ethylmaleimide conjugate. Growth assays of yeasts in the presence of cadmium (Cd) suggested that AtOPT6 may transport Cd and Cd/GSH conjugate. Reporter gene experiments showed that AtOPT6 is mainly expressed in dividing areas of the plant (cambium, areas of lateral root initiation). RNA blots on cell suspensions and real-time reverse transcription-PCR on Arabidopsis plants indicated that AtOPT6 expression is strongly induced by primisulfuron and, to a lesser extent, by abscisic acid but not by Cd. Altogether, the data show that the substrate specificity and the physiological functions of AtOPT members may be diverse. In addition to peptide transport, AtOPT6 is able to transport glutathione derivatives and metal complexes, and may be involved in stress resistance.As other eucaryotic cells and procaryotes, plant cells have the ability to transport peptides across membranes. Peptide transport is important for storage and mobilization of reduced nitrogen (Higgins and Payne, 1977), and it is also involved in a wide range of cellular processes, including quorum sensing in bacteria, yeast mating, and the immune response in mammals (Stacey et al., 2002b). Furthermore, peptide-derived antibiotics (Dantzig et al., 1992) and anticancer agents (Hori et al., 1993) are also transported by peptide transporters.The presence of multiple peptide transporters in the Arabidopsis genome and the known functions of peptide transport in bacteria, fungi, and animals suggest that peptide transporters may also play a key role in plant growth and development (Stacey et al., 2002a). Three gene families have been shown to transport various peptides in Arabidopsis, i.e. the peptide transporter (PTR) family, the oligopeptide transporter (OPT) family, and the multidrug resistance-associated protein (MRP) family.The Arabidopsis genome contains 51 PTR family members (Stacey et al., 2002a). AtPTR2, the best known member o...