Hgt1p, a high affinity glutathione transporter from the yeast Saccharomyces cerevisiae

A high affinity glutathione transporter has been identified, cloned, and ch aracterized from the yeast Saccharomyces cerevisiae, This transporter, Hgt1 p, represents the first high affinity glutathione transporter to be describ ed from any system so far. The strategy for the identification involved inv estigating candidate glutathione transporters from the yeast genome sequenc e project followed by genetic and physiological investigations. This approa ch revealed HGT1 (open reading frame YJL212c) as encoding a high affinity g lutathione transporter. Yeast strains deleted in HGT1 did not show any dete ctable plasma membrane glutathione transport, and hgt1 Delta disruptants we re non-viable in a glutathione biosynthetic mutant (gsh1 Delta) background. The glutathione repressible transport activity observed in wild type cells was also absent in the hgt1 Delta strains. The transporter was cloned and kinetic studies indicated that Hgt1p had a high affinity for glutathione (K -m = 54 mu M)) and was not sensitive to competition by amino acids, dipepti des, or other tripeptides. Significant inhibition was observed, however, wi th oxidized glutathione and glutathione conjugates, The transporter reveals a novel class of transporters that has homologues in other yeasts and plan ts but with no apparent homologues in either Escherichia coli or in higher eukaryotes other than plants.