YCF1-mediated cadmium resistance in yeast is dependent on copper metabolism and antioxidant enzymes.
OBJECTIVE
Acquisition and detoxification of metal ions are vital biological processes. Given the requirement of metallochaperones in cellular copper distribution and metallation of cuproproteins, this study investigates whether the metallochaperones also deliver metal ions for transporters functioning in metal detoxification.


RESULTS
Resistance to excess cadmium and copper of the yeast Saccharomyces cerevisiae, which is conferred by PCA1 and CaCRP1 metal efflux P-type ATPases, respectively, does not rely on known metallochaperones, Atx1p, Ccs1p, and Cox17p. Copper deficiency induced by the expression of CaCRP1 encoding a copper exporter occurs in the absence of Atx1p. Intriguingly, CCS1 encoding the copper chaperone for superoxide dismutase 1 (Sod1p) is necessary for cadmium resistance that is mediated by Ycf1p, a vacuolar cadmium sequestration transporter. This is attributed to Ccs1p's role in the maturation of Sod1p rather than its direct interaction with Ycf1p for cadmium transfer. Functional defect in Ycf1p associated with the absence of Sod1p as well as another antioxidant enzyme Glr1p is rescued by anaerobic growth or substitutions of specific cysteine residues of Ycf1p to alanine or serine. This further supports oxidative inactivation of Ycf1p in the absence of Ccs1p, Sod1p, or Glr1p.


METHODS
These results provide new insights into the mechanisms of metal metabolism, interaction among metal ions, and the roles for antioxidant systems in metal detoxification.


CONCLUSIONS
Copper metabolism and antioxidant enzymes maintain the function of Ycf1p for cadmium defense.
Department of Biochemistry, Redox Biology Center, University of Nebraska-Lincoln , Lincoln, Nebraska.
Wenzhong
W
Wei
Nathan
N
Smith
Xiaobin
X
Wu
Heejeong
H
Kim
Javier
J
Seravalli
Oleh
O
Khalimonchuk
Jaekwon
J
Lee
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000975:Antioxidants / Q000378:metabolism*; D002104:Cadmium / Q000633:toxicity*; D003300:Copper / Q000378:metabolism*; D025141:Drug Resistance, Fungal; D018384:Oxidative Stress; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D000975:Antioxidants; D029701:Saccharomyces cerevisiae Proteins; C089179:YCF1 protein, S cerevisiae; D002104:Cadmium; D003300:Copper; D013482:Superoxide Dismutase