A new pathway for vacuolar cadmium sequestration in Saccharomyces cerevisiae: YCF1-catalyzed transport of bis(glutathionato)cadmium.

Abstract

The yeast cadmium factor (YCF1) gene encodes an MgATP-energized glutathione S-conjugate transporter responsible for the vacuolar sequestration of organic compounds after their S-conjugation with glutathione. However, while YCF1 was originally isolated according to its ability to confer resistance to cadmium salts, neither its mode of interaction with Cd2+ nor the relationship between this process and organic glutathione-conjugate transport are known. Here we show through direct comparisons between vacuolar membrane vesicles purified from Saccharomyces cerevisiae strain DTY167, harboring a deletion of the YCF1 gene, and the isogenic wild-type strain DTY165 that YCF1 mediates the MgATP-energized vacuolar accumulation of Cd-glutathione complexes. The substrate requirements, kinetics and Cd2+/glutathione stoichiometry of cadmium uptake and the molecular weight of the transport-active complex demonstrate that YCF1 selectively catalyzes the transport of bis(glutathionato)cadmium (Cd x +GS2). On the basis of these results--the Cd2+ hypersensitivity of DTY167, versus DTY165, cells, the inducibility of YCF1-mediated transport, and the rapidity and spontaneity of Cd-GS2 formation--this new pathway is concluded to contribute substantially to Cd2+ detoxification.

• Authors: Z S Li, Y P Lu, R G Zhen, M Szczypka, D J Thiele, P A Rea
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 94 Issue 1 Pg. 42-7 (Jan 07 1997) ISSN: 0027-8424 [Print] United States
• PMID: 8990158 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ATP-Binding Cassette Transporters
• Dinitrochlorobenzene
• Fungal Proteins
• Organometallic Compounds
• Saccharomyces cerevisiae Proteins
• YCF1 protein, S cerevisiae
• bis(glutathionato)cadmium
• Cadmium
• S-(2,4-dinitrophenyl)glutathione
• Adenosine Triphosphate
• Glutathione

Topics

• ATP-Binding Cassette Transporters
• Adenosine Triphosphate (pharmacology)
• Biological Transport (drug effects)
• Cadmium (pharmacokinetics)
• Cell Compartmentation
• Dinitrochlorobenzene (pharmacology)
• Fungal Proteins (genetics, metabolism)
• Gene Deletion
• Gene Expression (drug effects)
• Glutathione (analogs & derivatives, metabolism, pharmacokinetics, pharmacology)
• Inactivation, Metabolic
• Organometallic Compounds (pharmacokinetics)
• Saccharomyces cerevisiae (metabolism)
• Saccharomyces cerevisiae Proteins
• Vacuoles (metabolism)