title: Characterization of a Plasmodium falciparum Orthologue of the Yeast Ubiquinone-Binding Protein, Coq10p.
abstract: 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.
authors.affiliation: Center for Molecular Parasitology, Drexel University College of Medicine, Philadelphia, PA, United States of America.
authors.forename: Bethany J
authors.initials: BJ
authors.lastname: Jenkins
authors.affiliation: Center for Molecular Parasitology, Drexel University College of Medicine, Philadelphia, PA, United States of America.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Daly
authors.affiliation: Center for Molecular Parasitology, Drexel University College of Medicine, Philadelphia, PA, United States of America.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Morrisey
authors.affiliation: Center for Molecular Parasitology, Drexel University College of Medicine, Philadelphia, PA, United States of America.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Mather
authors.affiliation: Center for Molecular Parasitology, Drexel University College of Medicine, Philadelphia, PA, United States of America.
authors.forename: Akhil B
authors.initials: AB
authors.lastname: Vaidya
authors.affiliation: Center for Molecular Parasitology, Drexel University College of Medicine, Philadelphia, PA, United States of America.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Bergman
mesh_terms: D053626:Atovaquone / Q000008:administration & dosage; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000235:genetics* / Q000469:parasitology; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics* / Q000472:pathogenicity; D012119:Respiration / Q000187:drug effects / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C027208:ubiquinone-binding proteins; D014451:Ubiquinone; C024989:coenzyme Q10; D053626:Atovaquone