@Article{IPB-2150, author = {Clemens, S. and Bloss, T. and Vess, C. and Neumann, D. and Nies, D. H. and zur Nieden, U.}, title = {{A Transporter in the Endoplasmic Reticulum of Schizosaccharomyces pombe Cells Mediates Zinc Storage and Differentially Affects Transition Metal Tolerance}}, year = {2002}, pages = {18215-18221}, journal = {J. Biol. Chem.}, doi = {10.1074/jbc.M201031200}, volume = {277}, abstract = {The cation diffusion facilitator (CDF) family represents a class of ubiquitous metal transporters. Inactivation of a CDF in Schizosaccharomyces pombe, Zhf, causes drastically different effects on the tolerance toward various metals. A deletion mutant is Zn2\+/Co2\+-hypersensitive yet displays significantly enhanced Cd2\+ and Ni2\+ tolerance. Accumulation of zinc, cobalt, and cadmium is reduced in mutant cells. Non-vacuolar zinc content, as measured by analytical electron microscopy, is lower in zhf− cells compared with wild-type cells in the presence of elevated Zn2\+concentrations. The protective effect against cadmium toxicity is independent of the phytochelatin detoxification pathway. Phytochelatin synthase-deficient cells show extremely enhanced (about 200-fold) cadmium tolerance when zhf is disrupted. Immunogold labeling indicates endoplasmic reticulum (ER) localization of Zhf. Electron spectroscopic imaging shows that accumulation of zinc coincides with Zhf localization, demonstrating a major role of the ER for metal storage and the involvement of Zhf in cellular zinc homeostasis. Also, these observations indicate that Cd2\+ions exert their toxic effects on cellular metabolism in the ER rather than in the cytosol.} }