Potassium and the K⁺/H⁺ exchanger Kha1p promote binding of copper to ApoFet3p multi-copper ferroxidase

Acquisition and distribution of metal ions support a number of biological processes. Here we show that respiratory growth of and iron acquisition by the yeast Saccharomyces cerevisiae relies on potassium (K⁺) compartmentalization to the trans-Golgi network via Kha1p, a K⁺/H⁺ exchanger. K⁺ in the trans-Golgi network facilitates binding of copper to the Fet3p multi-copper ferroxidase. The effect of K⁺ is not dependent on stable binding with Fet3p or alteration of the characteristics of the secretory pathway. The data suggest that K⁺ acts as a chemical factor in Fet3p maturation, a role similar to that of cations in folding of nucleic acids. Up-regulation of KHA1 gene in response to iron limitation via iron-specific transcription factors indicates that K⁺ compartmentalization is linked to cellular iron homeostasis. Our study reveals a novel functional role of K⁺ in the binding of copper to apoFet3p and identifies a K⁺/H⁺ exchanger at the secretory pathway as a new molecular factor associated with iron uptake in yeast.