Figure 2.

Copper homeostasis in fungi. Fungal cells generally encode two high-affinity copper importers, Ctr1 and Ctr3 (Ctr4), except in Candida albicans, which possesses only the Ctr1 homolog. Atx1 and Ccs are two copper chaperones, delivering copper to Ccc2 and Sod1, respectively. Metallothioneins (MTs) are copper detoxification proteins that bind excess copper. Ctr2 is a vacuolar copper transporter, pumping copper from the vacuolar space into the cytosol compartment. Mac1 controls the copper depletion responses of Saccharomyces cerevisiae and C. albicans by activating the expression of copper transporters. Saccharomyces cerevisiae Ace1 responds to copper toxicity and induces MT expression. C. neoformans Cuf1 controls responses in both copper-rich and copper-poor environments. Cuf1 constitutively binds to the promoter sequences of CFT1 and CFO1.