title: The gene ICS3 from the yeast Saccharomyces cerevisiae is involved in copper homeostasis dependent on extracellular pH.
abstract: In the yeast Saccharomyces cerevisiae, many genes are involved in the uptake, transport, storage and detoxification of copper. Large scale studies have noted that deletion of the gene ICS3 increases sensitivity to copper, Sortin 2 and acid exposure. Here, we report a study on the Δics3 strain, in which ICS3 is related to copper homeostasis, affecting the intracellular accumulation of this metal. This strain is sensitive to hydrogen peroxide and copper exposure, but not to other tested transition metals. At pH 6.0, the Δics3 strain accumulates a larger amount of intracellular copper than the wild-type strain, explaining the sensitivity to oxidants in this condition. Unexpectedly, sensitivity to copper exposure only occurs in acidic conditions. This can be explained by the fact that the exposure of Δics3 cells to high copper concentrations at pH 4.0 results in over-accumulation of copper and iron. Moreover, the expression of ICS3 increases in acidic pH, and this is correlated with CCC2 gene expression, since both genes are regulated by Rim101 from the pH regulon. CCC2 is also upregulated in Δics3 in acidic pH. Together, these data indicate that ICS3 is involved in copper homeostasis and is dependent on extracellular pH.
authors.affiliation: Departamento de Tecnologia Bioquímico-Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Brazil.
authors.forename: C A
authors.initials: CA
authors.lastname: Alesso
authors.affiliation: Departamento de Tecnologia Bioquímico-Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Brazil.
authors.forename: K F
authors.initials: KF
authors.lastname: Discola
authors.affiliation: Departamento de Tecnologia Bioquímico-Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Brazil. Electronic address: smgisele@usp.br.
authors.forename: G
authors.initials: G
authors.lastname: Monteiro
mesh_terms: D003300:Copper / Q000378:metabolism*; D005110:Extracellular Space; D015966:Gene Expression Regulation, Fungal; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D050296:Microbial Viability; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D003300:Copper
keywords: Acidic conditions; Copper accumulation; Copper homeostasis; pH dependent response