title: ABCC subfamily vacuolar transporters are involved in Pb (lead) detoxification in Saccharomyces cerevisiae.
abstract: The present work has as objective to contribute for the elucidation of the mechanism associated with Pb detoxification, using the yeast Saccharomyces cerevisiae as a model organism. The deletion of GTT1 or GTT2 genes, coding for functional glutathione transferases (GST) enzymes in S. cerevisiae, caused an increased susceptibility to high Pb concentrations (500-1000 μmol L(-1)). These results suggest that the formation of glutathione-Pb conjugate (GS-Pb), dependent of GSTs, is important in Pb detoxification. The involvement of ATP-binding cassette (ABC) vacuolar transporters, belonging to class C subfamily (ABCC) in vacuolar compartmentalization of Pb, was evaluated. For this purpose, mutant strains disrupted in YCF1, VMR1, YBT1 or BPT 1 genes were used. All mutants tested, without vacuolar ABCC transporters, presented an increased sensitivity to 500-1000 μmol L(-1) Pb comparative to wild-type strain. Taken together, the obtained results suggest that Pb detoxification, by vacuolar compartmentalization, can occur as a result of the concerted action of GSTs and vacuolar ABCC transporters. Pb is conjugated with glutathione, catalysed by glutathione transferases and followed to the transport of GS-Pb conjugate to the vacuole by ABCC transporters.
authors.affiliation: Bioengineering Laboratory-CIETI, Chemical Engineering Department, ISEP-School of Engineering of Polytechnic Institute of Porto, Rua Dr António Bernardino de Almeida, 431, 4200-072, Porto, Portugal.
authors.forename: Cátia A
authors.initials: CA
authors.lastname: Sousa
authors.forename: Simon
authors.initials: S
authors.lastname: Hanselaer
authors.forename: Eduardo V
authors.initials: EV
authors.lastname: Soares
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D007854:Lead / Q000378:metabolism / Q000633:toxicity; D050216:Metabolic Detoxication, Phase I; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000235:genetics / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D029701:Saccharomyces cerevisiae Proteins; C555911:Vmr1 protein, S cerevisiae; C106609:YBT1 protein, S cerevisiae; C089179:YCF1 protein, S cerevisiae; D007854:Lead; D005982:Glutathione Transferase; D005978:Glutathione