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Characterization of a Plasmodium falciparum Orthologue of the Yeast Ubiquinone-Binding Protein, Coq10p
Journal article   Open access   Peer reviewed

Characterization of a Plasmodium falciparum Orthologue of the Yeast Ubiquinone-Binding Protein, Coq10p

Bethany J Jenkins, Thomas M Daly, Joanne M Morrisey, Michael W Mather, Akhil B Vaidya and Lawrence W Bergman
PloS one, v 11(3), pp e0152197-e0152197
2016
PMID: 27015086
url
https://doi.org/10.1371/journal.pone.0152197View
Published, Version of Record (VoR)CC BY V4.0 Open

Abstract

Atovaquone - administration & dosage Carrier Proteins - biosynthesis Carrier Proteins - genetics Gene Expression Regulation - drug effects Humans Malaria, Falciparum - drug therapy Malaria, Falciparum - genetics Malaria, Falciparum - parasitology Mitochondria - drug effects Mitochondria - genetics Plasmodium falciparum - genetics Plasmodium falciparum - pathogenicity Respiration - drug effects Respiration - genetics Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - growth & development Ubiquinone - analogs & derivatives Ubiquinone - biosynthesis Ubiquinone - deficiency Ubiquinone - genetics
Coenzyme Q (CoQ, ubiquinone) is a central electron carrier in mitochondrial respiration. CoQ is synthesized through multiple steps involving a number of different enzymes. The prevailing view that the CoQ used in respiration exists as a free pool that diffuses throughout the mitochondrial inner membrane bilayer has recently been challenged. In the yeast Saccharomyces cerevisiae, deletion of the gene encoding Coq10p results in respiration deficiency without inhibiting the synthesis of CoQ, suggesting that the Coq10 protein is critical for the delivery of CoQ to the site(s) of respiration. The precise mechanism by which this is achieved remains unknown at present. We have identified a Plasmodium orthologue of Coq10 (PfCoq10), which is predominantly expressed in trophozoite-stage parasites, and localizes to the parasite mitochondrion. Expression of PfCoq10 in the S. cerevisiae coq10 deletion strain restored the capability of the yeast to grow on respiratory substrates, suggesting a remarkable functional conservation of this protein over a vast evolutionary distance, and despite a relatively low level of amino acid sequence identity. As the antimalarial drug atovaquone acts as a competitive inhibitor of CoQ, we assessed whether over-expression of PfCoq10 altered the atovaquone sensitivity in parasites and in yeast mitochondria, but found no alteration of its activity.

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Web of Science research areas
Biochemistry & Molecular Biology
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