Acidification of the malaria parasite's digestive vacuole by a H+-ATPase and a H+-pyrophosphatase

Kevin J. Saliba*, Richard J.W. Allen, Stephanie Zissis, Patrick G. Bray, Stephen A. Ward, Kiaran Kirk

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    109 Citations (Scopus)

    Abstract

    As it grows within the human erythrocyte, the malaria parasite, Plasmodium falciparum, ingests the erythrocyte cytosol, depositing it via an endocytotic feeding mechanism in the "digestive vacuole," a specialized acidic organelle. The digestive vacuole is the site of hemoglobin degradation, the storage site for hemozoin (an inert biocrystal of toxic heme), the site of action of many antimalarial drugs, and the site of proteins known to be involved in antimalarial drug resistance. The acidic pH of this organelle is thought to play a critical role in its various functions; however, the mechanisms by which the pH within the vacuole is maintained are not well understood. In this study, we have used a combination of techniques to demonstrate the presence on the P. falciparum digestive vacuole membrane of two discrete H+ pumping mechanisms, both capable of acidifying the vacuole interior. One is a V-type H+-ATPase, sensitive to concanamycin A and bafilomycin A1. The other is a H+-pyrophosphatase, which was inhibited by NaF and showed a partial dependence on K+. The operation of the H+-pyrophosphatase was dependent on the presence of a Mg2+-pyrophosphate complex, and kinetic experiments gave results consistent with free pyrophosphate acting as an inhibitor of the protein. The presence of the combination of a H+-ATPase and a H+-pyrophosphatase on the P. falciparum digestive vacuole is similar to the situation in the acidic tonoplasts (vacuoles) of plant cells.

    Original languageEnglish
    Pages (from-to)5605-5612
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume278
    Issue number8
    DOIs
    Publication statusPublished - 21 Feb 2003

    Fingerprint

    Dive into the research topics of 'Acidification of the malaria parasite's digestive vacuole by a H+-ATPase and a H+-pyrophosphatase'. Together they form a unique fingerprint.

    Cite this