Role of the yeast multidrug transporter Qdr2 in cation homeostasis and the oxidative stress response

Authors

  • Gabino Ríos,

    1. Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de València-CSIC, Valencia, Spain
    Current affiliation:
    1. Instituto Valenciano de Investigaciones Agrarias (IVIA), Moncada, Valencia, Spain
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  • Marc Cabedo,

    1. Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de València-CSIC, Valencia, Spain
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  • Baltasar Rull,

    1. Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de València-CSIC, Valencia, Spain
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  • Lynne Yenush,

    1. Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de València-CSIC, Valencia, Spain
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  • Ramón Serrano,

    1. Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de València-CSIC, Valencia, Spain
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  • José M. Mulet

    Corresponding author
    • Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de València-CSIC, Valencia, Spain
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Correspondence: José M. Mulet, IBMCP, Universitat Politècnica de València, Camino de Vera S/N, 46022 Valencia, Spain. Tel.: +34 96 3877775; fax: +34 96 3877859; e-mail: jmmulet@ibmcp.upv.es

Abstract

We have identified QDR2 in a screening for genes able to confer tolerance to sodium and/or lithium stress upon overexpression. Qdr2 is a multidrug transporter of the major facilitator superfamily, originally described for its ability to transport the antimalarial drug quinidine and the herbicide barban. To identify its physiological substrate, we have screened for phenotypes dependent on QDR2 and found that Qdr2 is able to transport monovalent and divalent cations with poor selectivity, as shown by growth tests and the determination of internal cation content. Moreover, strains overexpressing or lacking QDR2 also exhibit phenotypes when reactive oxygen species- producing agents, such as hydrogen peroxide or menadione were added to the growth medium. We have also found that the presence of copper and hydrogen peroxide repress the expression of QDR2. In addition, the copper uptake of a qdr2 mutant strain is similar to a wild type, but the extrusion is clearly impaired. Based on our results, we propose that free divalent copper is the main physiological substrate of Qdr2. As copper is a substrate for several redox reactions that occur within the cytoplasm, its function in copper homeostasis explains its role in the oxidative stress response.

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