title: Mitochondrial dehydrogenases in the aerobic respiratory chain of the rodent malaria parasite Plasmodium yoelii yoelii.
abstract: In the intraerythrocytic stages of malaria parasites, mitochondria lack obvious cristae and are assumed to derive energy through glycolysis. For understanding of parasite energy metabolism in mammalian hosts, we isolated rodent malaria mitochondria from Plasmodium yoelii yoelii grown in mice. As potential targets for antiplasmodial agents, we characterized two respiratory dehydrogenases, succinate:ubiquinone reductase (complex II) and alternative NADH dehydrogenase (NDH-II), which is absent in mammalian mitochondria. We found that P. y. yoelii complex II was a four-subunit enzyme and that kinetic properties were similar to those of mammalian enzymes, indicating that the Plasmodium complex II is favourable in catalysing the forward reaction of tricarboxylic acid cycle. Notably, Plasmodium complex II showed IC(50) value for atpenin A5 three-order of magnitudes higher than those of mammalian enzymes. Divergence of protist membrane anchor subunits from eukaryotic orthologs likely affects the inhibitor resistance. Kinetic properties and sensitivity to 2-heptyl-4-hydroxyquinoline-N-oxide and aurachin C of NADH: ubiquinone reductase activity of Plasmodium NDH-II were similar to those of plant and fungus enzymes but it can oxidize NADPH and deamino-NADH. Our findings are consistent with the notion that rodent malaria mitochondria are fully capable of oxidative phosphorylation and that these mitochondrial enzymes are potential targets for new antiplasmodials.
authors.affiliation: Department of Biomedical Chemistry, Graduate School of Medicine, the University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawahara
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Mogi
authors.forename: Takeshi Q
authors.initials: TQ
authors.lastname: Tanaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hata
authors.forename: Hideto
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kita
mesh_terms: D000818:Animals; D004579:Electron Transport; D042963:Electron Transport Complex II / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D008288:Malaria / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010967:Plasmodium yoelii / Q000201:enzymology* / Q000378:metabolism / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats
chemical_list: D015800:Protozoan Proteins; D042963:Electron Transport Complex II; D009245:NADH Dehydrogenase