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Journal of Biochemistry Advance Access published online on December 6, 2008
Journal of Biochemistry, doi:10.1093/jb/mvn161
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© The authors 2008. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Mitochondrial Dehydrogenases in the Aerobic Respiratory Chain of the Rodent Malaria Parasite Plasmodium yoelii yoelii

Kenji Kawahara1, Tatsushi Mogi1,*, Takeshi Q Tanaka1, Masayuki Hata1, Hideto Miyoshi2 and Kiyoshi Kita1,*

1Department of Biomedical Chemistry, Graduate School of Medicine, the University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033; and 2Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan

*To whom correspondence addressed. Kiyoshi Kita Department of Biomedical Chemistry, Graduate School of Medicine, the University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Tel: +81 3 5841 3526, Fax: +81 3 5841 3444, E-mail: tmogi{at}m.u-tokyo.ac.jp, kitak{at}m.u-tokyo.ac.jp.

Received October 7, 2008; Accepted November 19, 2008


  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 favorable in catalyzing the forward reaction of tricarboxylic acid cycle. Notably, Plasmodium Complex II showed IC50 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.

Key Words: rodent malaria, mitochondria, Complex II, NDH-II, inhibitor


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