Figure 1. Copper pathways in Saccharomyces cerevisiae.

Copper fluxes are represented by blue arrows. Regulatory loops are indicated in red (activation) and green (repression). Monovalent and divalent Cu are represented by dark blue and light blue circles, respectively. The first step of Cu import is the reduction of Cu(II) to Cu(I) by the Fre reductases, followed by the import through either high-affinity transporters represented in green (Ctr1p) and blue (Ctr3p) or low-affinity transporters such as Fet proteins (red). Copper is subsequently transported in the different compartments of the cell cytoplasm by different protein chaperones such as Ccsp, ATX1 or ccc2. Copper transport is regulated by MAC1 which senses high intracellular Cu concentrations and down regulates the expression of the high-affinity transporters CTR1 and CTR3 and of the reductase FRE1, while it activates the expression of the FRE2 reductase³,¹⁴,¹⁵,¹⁶,¹⁷,¹⁸,²¹,²²,²³,²⁴,²⁵,⁵².