The Multidrug Resistance-associated Protein (MRP) Subfamily (Yrs1/Yor1) of Is Important for the Tolerance to a Broad Range of Organic Anions

Abstract

We have cloned and characterized a Saccharomyces cerevisiae gene YRS1 that complements the phenotype of the mutant sensitive to the anionic drug reveromycin A. The YRS1 gene, which is identical to the recently identified YOR1 gene, encodes a protein with extensive homology to the human multidrug resistance-associated protein (MRP) and the yeast cadmium factor (Ycf1). A chromosomal deletion of YRS1 lead to viable Deltayrs1 cells, which exhibited hypersensitivity to reveromycin A. Elevation of the YRS1 gene dosage in wild type cells conferred increased resistance to reveromycin A. By analyzing the effect of YRS1 disruption and overexpression it was demonstrated that Yrs1 is involved in the detoxification of a wide range of the organic anions that contain carboxyl group(s) but none of the other type of toxic compounds examined. Fluorescence-activated cell sorter analysis indicated the increased accumulation of the anionic fluorescent compound rhodamine B in Deltayrs1 cells. The expression of YRS1 was induced strikingly by reveromycin A. These results suggest that Yrs1 is a multispecific organic anion transporter important for tolerance against toxic environmental organic anions. Yrs1 had an overlapping specificity with Ycf1 in the resistance to cadmium.

A Novel Membrane-bound Glutathione S-Transferase Functions in the Stationary Phase of the Yeast Saccharomyces cerevisiae

“…40 -42), the yeast cadmium factor protein (Ycf1p; Refs. 14 -16, 43, and 44) and possibly the yeast Yor1p protein (45). Through the concerted actions of GSTs and the GS-X pumps, cells can confer a common structural determinant on toxins, increase their water solubility, and then eliminate them from the cytosol (1,46).…”

ABC Transporters in Saccharomyces cerevisiae and Their Interactors: New Technology Advances the Biology of the ABCC (MRP) Subfamily

“…The name Yor1p (for yeast oligomycin resistance) reflects that fact that the YOR1 gene was discovered based on its ability to confer resistance to the mitochondrial poison oligomycin when overexpressed and to confer sensitivity when deleted (76). Early on, Yor1p overexpression was also shown to confer resistance to the anionic antifungal drug reveromycin A and the anionic fluorescent compound rhodamine B, leading to the suggestion that Yor1p was a multispecific organic anion transporter (23). However, a large-scale study of several hundred compounds identified many more Yor1p substrates and indicated that Yor1p could transport an impressive variety of compounds with quite distinct chemical features (85,134).…”

The Yeast Genes ROX1, IXR1, SKY1 and Their Effect upon Enzymatic Activities Related to Oxidative Stress

“…As (III) is exported by the Acr3 transporter (Ghosh et al, 1999;Wysocki et al, 1997). It has been proposed that Yor1 mediates Cd (II) efflux in the form of Cd (GS) 2 (Cui et al, 1996;Nagy et al, 2006). Cd (II) and As (III) GSH-conjugates are imported into vacuole by Ycf1.…”