Potassium and the K⁺/H⁺ Exchanger Kha1p Promote Binding of Copper to ApoFet3p Multi-copper Ferroxidase

Authors

Xiaobin Wu, University of Nebraska-Lincoln
Heejeong Kim, University of Nebraska-LincolnFollow
Javier Seravalli, University of Nebraska-LincolnFollow
Joseph J. Barycki, University of Nebraska - LincolnFollow
P. John Hart, University of Texas Health Science Center
David W. Gohara, Saint Louis University School of Medicine
Enrico Di Cera, Saint Louis University School of Medicine
Won Hee Jung, Chung-Ang University
Daniel J. Kosman, University at Buffalo
Jaekwon Lee, University of Nebraska - LincolnFollow

Document Type

Article

Date of this Version

2016

Citation

THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 291, NO. 18, pp. 9796–9806, April 29, 2016

Comments

© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Abstract

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.