Copper Transport in Fungi

Abstract

A clear understanding of copper metabolism is critical because copper is absolutely essential but also toxic. Significant new knowledge in this field was achieved through research using yeast models, including Saccharomyces cerevisiae and Schizosaccharomyces pombe . Both yeasts are highly needed model organisms for identifying the molecular mechanisms whereby cells appropriately acquire copper and regulate gene expression in response to changes in copper levels. This article summarizes our current understanding of a number of components involved in copper uptake, trafficking, compartmentalization, and copper sensing to establish and maintain normal copper homeostasis.

Copper transport and regulation in Schizosaccharomyces pombe

“…In the case of S. pombe , Pccs, Cox17 and Atx1 serve as copper chaperones to deliver copper to cytosolic Sod1, mitochondrial Cco and cytosolic Cao1 respectively. Furthermore, Atx1 carries copper to the secretory compartment by docking specifically with the Ccc2 copper-transporting P-type ATPase [12–14] (Figure 1). …”

“…Ctr4, Ctr5 and Ctr6) in S. pombe , under conditions of low intracellular levels of copper [4,5,15,17,18]. In contrast, when cells are grown in the presence of high levels of copper, Cuf1 is unable to bind chromatin, which results in repression of the ctr4 + , ctr5 + and ctr6 + genes [14]. cuf1 Δ mutant cells exhibit phenotypes typical of copper insufficiency, including inability to transport copper, failure to grow on respiratory carbon sources owing to the lack of copper incorporation into Cco, and impaired Sod1 and Cao activities.…”

“…In vitro binding studies have revealed that a recombinant protein containing residues 1–174 of Cuf1 binds CuSEs [19]. Further analysis, using chromatin immunoprecipitation assays in S. pombe , have revealed that Cuf1 binds to the CuSEs-containing ctr4 + promoter in vivo under copper-limiting conditions [14]. In contrast, Cuf1 is released from the ctr4 + promoter under conditions of high copper concentrations, resulting in inactivation of ctr4 + gene expression.…”