Cadmium regulates copper homoeostasis by inhibiting the activity of Mac1, a transcriptional activator of the copper regulon, in Saccharomyces cerevisiae

Abstract

Cadmium is a toxic metal and the mechanism of its toxicity has been studied in various model systems from bacteria to mammals. We employed Saccharomyces cerevisiae as a model system to study cadmium toxicity at the molecular level because it has been used to identify the molecular mechanisms of toxicity found in higher organisms. cDNA microarray and Northern blot analyses revealed that cadmium salts inhibited the expression of genes related to copper metabolism. Western blotting, Northern blotting and chromatin immunoprecipitation experiments indicated that CTR1 expression was inhibited at the transcriptional level through direct inhibition of the Mac1 transcriptional activator. The decreased expression of CTR1 results in cellular copper deficiency and inhibition of Fet3 activity, which eventually impairs iron uptake. In this way, cadmium exhibits a negative effect on both iron and copper homoeostasis.

Effects of cadmium on intracellular cation homoeostasis in the yeastSaccharomyces cerevisiae

“…In S. cerevisiae, ion homoeostasis is regulated by ion uptake across the plasma membrane. It has been reported that several ion channels are involved in the uptake and intracellular transport of cadmium, which could be transported into cells through bivalent cation transporters (Diffels et al 2006;Liu and Templeton 2007;Heo et al 2010;K€ upper and Leitenmaier 2013). In aqueous solution, Cd 2C and Ca 2C have similar ionic radii; consequently, several proteins containing Ca 2C binding motifs can also bind Cd 2C (Liu and X.…”

Cd2+ binds to Atx1 and affects the physical interaction between Atx1 and Ccc2 in Saccharomyces cerevisiae

“…We have previously reported that the copper and iron transport pathway is crucial for Cd 2? toxicity (Heo et al 2010). As shown in Fig.…”

“…toxicity and provides evidence of competition between copper and Cd 2? (Heo et al 2010). In the present study, we demonstrated the role of Atx1 in Cd 2?…”

“…and Cd 2? (Heo et al 2010). In S. cerevisiae, copper is delivered by cellular chaperones, such as Atx1, Ccs and Cox17, to target proteins in cytosolic compartments (Beers et al 1997;Culotta et al 1997;Glerum et al 1996;Lin and Culotta 1995).…”

IK Induced by Coxsackievirus B3 Infection Transiently Downregulates Expression of MHC Class II Through Increasing cAMP

“…Yeast two-hybrid assay A yeast two-hybrid assay was performed using the PBN204 yeast strain, as described previously (16). The cDNA library was from human T cells and was purchased from Clontech (Mountain View, CA).…”