New insights into the Ca2+-ATPases that contribute to cadmium tolerance in yeast

Abstract

Cadmium (Cd(2+)) is a toxic heavy metal which triggers several toxic effects in eukaryotes, including neurotoxicity and impaired calcium metabolism. In the model organism Saccharomyces cerevisiae, the best characterized pathway for Cd(2+) detoxification involves conjugation with glutathione (GSH) and subsequent transport to vacuoles by Ycf1p, an ATPase homologous to human MRP1 (Multidrug resistance associated protein 1). However, Cd(2+) tolerance also can be mediated by Pmr1p, a Ca(2+) pump located in the Golgi membrane, possibly through to the secretory pathway. Herein, we showed that inactivation of the PMR1 gene, alone or simultaneously with YCF1, delayed initial Cd(2+) capture compared to wild-type (WT) cells. In addition, Cd(2+) treatment altered the expression profile of yeast internal Ca(2+) transporters; specifically, PMC1 gene expression is induced substantially by the metal in WT cells, and this induction is stronger in mutants lacking YCF1. Taken together, these results indicate that, in addition to Pmr1p, the vacuolar Ca(2+)-ATPase Pmc1p also helps yeast cells cope with Cd(2+) toxicity. We propose a model where Pmc1p and Pmr1p Ca(2+)-ATPase function in cooperation with Ycf1p to promote Cd(2+) detoxification.

Effects of cadmium on intracellular cation homoeostasis in the yeastSaccharomyces cerevisiae

“…It suggests that PMR1, ZRT1, CTR1, FET3, and TRK1 are involved in the cellular detoxification of cadmium. Since cadmium can bind to Pmr1p and be transported to the Golgi and excreted extracellularly by vesicles of the exocytic pathway (Lauer-J unior et al 2008;Mielniczki-Pereira et al 2011), our data confirmed the involvement of PMR1 to Cd 2C detoxification. Previous reports have shown that cadmium uptake is reduced by increasing the calcium concentration of the medium (Ardestani, Ortiz, and van Gestel 2013), which was confirmed by our data that the addition of Ca 2C distinctly attenuated the growth inhibition of cadmium to cells.…”

“…Some previous studies have shown that cadmium can affect transporters of some essential cations and trace elements in yeast cells (Gomes et al 2002;Mielniczki-Pereira et al 2011). However, the influence of cadmium on intracellular ion balance is still obscure.…”

Components of the Calcium-Calcineurin Signaling Pathway in Fungal Cells and Their Potential as Antifungal Targets

“…Many reports have demonstrated that VCX1, YVC1, PMC1, and PMR1 are involved in the tolerance and virulence of a variety of fungi, such as Cryptococcus neoformans, Saccharomyces cerevisiae, and Aspergillus fumigatus (51,88,89).…”

Overexpression of OLE1 Enhances Cytoplasmic Membrane Stability and Confers Resistance to Cadmium in Saccharomyces cerevisiae

“…Several microorganisms, such as yeast and bacteria, have been investigated for their use in different environments for metal toxicity treatment and control (6). One of the most commonly used models in such investigations is yeast.…”