Unique Properties of Respiratory Chain in Plasmodium Falciparum Mitochondria

  • Fumika Mi-Ichi
  • Satoru Takeo
  • Eizo Takashima
  • Tamaki Kobayashi
  • Hye-Sook Kim
  • Yusuke Wataya
  • Akira Matsuda
  • Motomi Torii
  • Takafumi Tsuboi
  • Kiyoshi Kita
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 531)


Malaria is one of the most serious infectious diseases in the developing world with a mortality rate of more than 1 million deaths per year. It is mainly caused by the erythrocytic stage cells of the parasite Plasmodium falciparum (WHO, 1997). Because drug-resistant parasites are now widespread, the development of new anti-malarial drugs is urgently required (011iario and Trigg, 1995).


Respiratory Chain Antimalarial Drug Succinate Dehydrogenase Trypanosoma Brucei Plasmodium Berghei 
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  1. Amino, H., Wang, H., Hirawake, H., Saruta, F., Mizuchi, D., Mineki, R., Shindo, N., Murayama, K., Takamiya, S., Aoki, T., Kojima, S., and Kita, K., 2000, Stage-specific isoforms of Ascaris suum complex II: the fumarate reductase of the parasitic adult and the succinate dehydrogenase of free-living larvae share a common iron-sulfur subunit. Mol. Biochem. Parasitol. 106 63–76.PubMedCrossRefGoogle Scholar
  2. Bannister, L.H., Hopkins, J.M., Fowler, R.E., Krishna, S., and Michell, G.H., 2000, A brief illustrated guide to the ultrastructure of Plasmodium falciparum asexual blood stages. Parasitol. Today 16 427–433.PubMedCrossRefGoogle Scholar
  3. Clarkson, A.B.Jr, Bienen, E.J., Pollakis, G., and Grady, R.W., 1989, Respiration of bloodstream forms of the parasite Trypanosoma brucei is dependent on a plant-like alternative oxidase. J. Biol. Chem. 264, 17770–17776.PubMedGoogle Scholar
  4. Cole, S.T., 1987, Nucleotide sequence and comparative analysis of the frd operon encoding the fumarate reductase of Proteus vulgaris. Eur. J. Biochem. 167 481–488.PubMedCrossRefGoogle Scholar
  5. Cole, S.T., Grundström, T., Jaulin, B., Robinson, J.J., and Weiner, J.H., 1982, Location and nucleotide sequence of frdB, the gene coding for the iron-sulphur protein subunit of the fumarate reductase of Escherichia coli. Eur. J. Biochem., 126 211–216.PubMedCrossRefGoogle Scholar
  6. Divo, A.A., Geary, T.G., Jensen, J.B., and Ginsburg, H., 1985, The mitochondrion of plasmodium falciparum visualized by rhodamine 123 fluorescence. J. Protozool. 32: 442–446.PubMedGoogle Scholar
  7. Ellis, J.E., 1994, Coenzyme Q homologs in parasitic protozoa as targets of chemotherapeutic attack. Parasitol. Today 10 296–301.PubMedCrossRefGoogle Scholar
  8. Feagin, J.E., 1992, The 6-kb element of Plasmodium falciparum encodes mitochondria! cytochrome genes. Mol. Biochem. Parasitol. 52 145–148.PubMedCrossRefGoogle Scholar
  9. Feagan, J.E., 1994, The extrachromosomal DNAs of apicomplexan parasites. Annu Rev. Microbiol. 48 81–104.CrossRefGoogle Scholar
  10. Fry, M., and Beesley, J.E., 1991, Mitochondria of mammalian Plasmodium spp. Parasitology 102 17–26.PubMedCrossRefGoogle Scholar
  11. Hirawake, H., Wang, H., Kuramochi, T., Kojima, S., and Kita, K., 1994, Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the flavoprotein (Fp) subunit of liver mitochondria. J. Biochem. 116 221–227.PubMedGoogle Scholar
  12. Howells, R.E., 1970, Mitochondrial changes during the life cycle of Plasmodium berghei. Annals Trop. Med. Parasitol. 64 181–187.Google Scholar
  13. Hägerhäll, C., 1997, Succinate:quinone oxidoreductases. Variations on a conserved theme. Biochim. Biophys. Acta 1320 107–141.PubMedCrossRefGoogle Scholar
  14. Iverson, T.M., Luna-Chavez, C., Cecchini, G., and Rees, D.C., 1999, Structure of the Escherichia coli fumarate reductase respiratory complex. Science, 284 1961–1966.PubMedCrossRefGoogle Scholar
  15. Jomaa, H., Wiesner, L., Sanderbrand, S., Altincicek, B., Weidemeyer, C., Hintz, M., Turbachova, I., Eberl, M., Zeidler, J., Lichtenthaler, H.K., Soldati, D., and Beck, E., 1999, Inhibitors of the non-mevalonate pathway of isoprenoid biosynthesis as antimalarial drug. Science, 285 1573–1576.PubMedCrossRefGoogle Scholar
  16. Kim, H.-S., Shibata, Y., Wataya, Y., Tsuchiya, K., Masuyama, A., and Nojima, M., 1999, Synthesis and antimalarial activity of cyclic peroxides, 1,2,4,5,7-pentoxocanes and 1,2,4,5-tetroxanes. J. Med. Chem. 42 2604–2609.PubMedCrossRefGoogle Scholar
  17. Kita, K., Hirawake, H., and Takamiya, S., 1997, Cytochromes in the respiratory chain of helminth mitochondria. Int. J. Parasitol. 27 617–630.PubMedCrossRefGoogle Scholar
  18. Kita, K., Hirawake, H., Miyadera, H., Amino, H., and Takeo, S., 2002, Role of complex II in anaerobic respiration of the parasite mitochondria from Ascaris suum and Plasmodium falciparum. Biochim. Biophys. Acta,1553 123–139.PubMedCrossRefGoogle Scholar
  19. Krungkrai, J., 1995, Purification, characterization and localization of mitochondrial dihydroorotate dehydrogenase in Plasmodium falciparum, human malaria parasites. Biochim. Biophys. Acta 1243 351–360.PubMedCrossRefGoogle Scholar
  20. Krungkrai, J., Krungkrai, A.R. and Bhumiratana, A., 1993, Plasmodium berghei partial purification and characterization of the mitochondrial cytochrome C oxidase. Exp. Parasitol. 77 136–146.PubMedCrossRefGoogle Scholar
  21. Krungkrai, J., Krungkrai, S.R., Suraveratum, N., and Prapunwattana, P., 1997, Mitochondrial ubiquinol-cytochrome c reductase and cytochrome c oxidase: chemotherapeutic targets in malarial parasites. Biochem. Mol. Biol. Int. 42 1007–1014.PubMedGoogle Scholar
  22. Krungkrai, J., Prapunwattana, P., and Krungkrai, S.R., 2000, Ultrastructure and function of mitochondria in gametocytic stage of Plasmodium falciparum. Parasite 7: 19–26.PubMedGoogle Scholar
  23. Krungkrai, J., Kanchnarithisak, R., Krungkrai, S.R., and Rochanakij, S., 2002, Mitochondrial NADH dehydrogenase from Plasmodium falciparum and Plasmodium berghei. Exp. Parasitol. 100 54–61.PubMedCrossRefGoogle Scholar
  24. Kuramochi, T., Hirawake, H., Kojima, S., Takamiya, S., Furushima, R., Aoki, T., Komuniecki, R., and Kita, K., 1994 Sequence comparison between the flavoprotein subunit of the fumarate reductase (complex II) of the anaerobicparasitic nematode, Ascaris suum and the succinate dehydrogenase of the aerobic, free-living nematode, Caenorhabditis elegans. Mol. Biochem. Parasitol. 68 177–187.PubMedCrossRefGoogle Scholar
  25. Köhler, S., Delwiche, C.F., Denny, P.W., Tilney, L.G., Webster, P., Wilson, R.J.M., Palmer, J.D., and Roos, D.S., 1997, A plastid of probable green algal origin in apicomplexan parasites. Science 275 1485–1489.PubMedCrossRefGoogle Scholar
  26. Lancaster, C.R.D., Kröger, A., Auer, M., and Michel, H., 1999, Structure of fumarate reductase from Wolinella succinogenes at 2.2Å resolution. Nature 402 377–385.PubMedCrossRefGoogle Scholar
  27. Lancaster, C.R.D. ed., 2002, Biochim. Biophys. Acta, 1553, Special issue on complex II.Google Scholar
  28. Lithgow, T., 2000, Targeting of proteins to mitochondria. FEBS Lett. 476 22–26.PubMedCrossRefGoogle Scholar
  29. Looareesuwan, S., Viravan, C., Webster, H.K., Kyle, D.E., Hutchinson, D.B., and Canfield, C.J., 1996, Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. Am. J. Trop. Med. Hyg. 54 62–66.PubMedGoogle Scholar
  30. McFadden, D.C., Tomavo, S., Berry, E.A., and Boothroyd, J.C., 2000, Characterization of cytochrome b from Toxoplasma gondii and Qo domain mutations as a mechanism of atovaquone-resistance. Mol. Biochem. Parasitol. 108 1–12.PubMedCrossRefGoogle Scholar
  31. Meis, J.F.G.M., Verhave J.P., Wirtz, P., and Meuwissen, J.H.E.T., 1984, Histochemical observations on the exoerythrocytic malaria parasite Plasmodium berghei in rat liver. Histochemistry 81 417–425.PubMedCrossRefGoogle Scholar
  32. Minagawa, N., Yabu, Y., Kita, K., Ohta, N., Meguro, K., Sakajo, S., and Yoshimoto, A., 1996, An antibiotic, ascofuranone, specifically inhibits respiration and in vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei. Mol. Biochem. Parasitol. 81 127–136.PubMedCrossRefGoogle Scholar
  33. Nihei, C., Fukai, Y., and Kita, K., 2002, Trypanosome alternative oxidase as a target of chemotherapy. Biochim. Biophys. Acta, in press.Google Scholar
  34. Ohnishi, T., Moser, C.C., Page, C.C., Dutton, P.L., and Yano, T., 2000, Simple redox-linked proton-transfer design: new insights from structures of quinol-umarate reductase. Structure Folding Design 8 R23–R32.CrossRefGoogle Scholar
  35. lliario, P., and Trigg, P.I., 1995, Status of antimalarial drugs under development. Bull. WHO 73: 565–571.Google Scholar
  36. Omura, S., Miyadera, H., Ui, H., Shiomi, K., Yamaguch, Y., Masuma, R., Nagamitsu, T., Takano, D., Sunazuka, T., Harder, A., Kölbl, H., Namikoshi, M., Miyoshi, H., Sakamoto, K., and Kita, K., 2001, An anthelmintic compound, nafuredin, shows selective inhibition of complex I in helminth mitochondria. Proc. Natl. Acad. Sci. USA 98 60–62.PubMedCrossRefGoogle Scholar
  37. Opperdoes, F.R., 1999, Carbohydrate metabolism. In Progress in Human African Trypanosomiasis, Sleeping Sickness (M. Dumas, B. Bouteille, and A. Buguet, eds.), Springer, Paris, pp. 53–80.Google Scholar
  38. Priest, J.W., and Hajduk, S.L., 1994, Developmental regulation of mitochondrial biogenesis in Trypanosoma brucei. J. Bioenerg. Biomembr. 26 179–191.PubMedCrossRefGoogle Scholar
  39. Robinson, K.M., and Lemire, B.D., 1992, Isolation and nucleotide sequence of the Saccharomyces cerevisiae gene for the succinate dehydrogenase flavoprotein subunit. J. Biol. Chem. 267 10101–10107.PubMedGoogle Scholar
  40. Saruta, F., Kuramochi, T., Nakamura, K., Takamiya, S., Yu, Y., Aoki, T., Sekimizu, K., Kojima, S., and Kita, K., 1995, Stage-specific isoforms of complex II (succinateubiquinone oxidoreductase) in mitochondria from the parasitic nematode, Ascaris suum. J. Biot. Chem. 270 928–932.Google Scholar
  41. Scheibel, L.W., Adler, A., and Trager, W., 1979, Tetraethylthiuram disulfide (Antabuse) inhibits the human malaria parasite Plasmodium falciparum . Proc.Natl. Acad. Sci. USA. 76 5303–5307.PubMedCrossRefGoogle Scholar
  42. Sherman, I.W., 1979, Biochemistry of Plasmodium (Malaria parasite). Microbiol. Rev. 43 453–495.PubMedGoogle Scholar
  43. Sherman, I.W., 1998, Carbohydrate metabolism of asexual stages. In Malaria (LW. Sherman, ed.), ASM Press, Washington, D.C., pp. 135–143.Google Scholar
  44. Srivastava, I.K., Rottenberg, H., and Vaidya, A.B., 1997, Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in malarial parasite. J. Biol. Chem. 272 3961–3966.PubMedCrossRefGoogle Scholar
  45. Srivastava, I.K., Morrisey, J.M., Darrouzet, E., Daldal, F., and Vaidya, A.B., 1999, Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. Mol. Microbiol. 33 704–711.PubMedCrossRefGoogle Scholar
  46. Suraveratum, N., Krungkrai, S.R., Leangaramgul, P., Prapunwattana, P., and Krungkrai, J., 2000, Purification and characterization of Plasmodium falciparum succinate dehydrogenase. Mol. Biochem. Parasitol. 105 215–222.PubMedCrossRefGoogle Scholar
  47. Takashima, E., Takamiya, S., Takeo, S., Mi-ichi, F., Amino, H., and Kita, K., 2001, Isolation of mitochondria from Plasmodium falciparum showing dihydroorotate dependent respiration. Parasitol. Int. 50 273–278.PubMedCrossRefGoogle Scholar
  48. Takeo, S., Kokaze, A., Ng, C.S., Mizuchi, D., Watanabe, J., Tanabe, K., Kojima, S., and Kita, K., 2000, Succinate dehydrogenase in Plasmodium falciparum mitochondria: molecular characterization of the SDHA and SDHB genes for the catalytic subunits, the flavoprotein (Fp) and iron-sulfur (Ip) subunits. Mol. Biochem. Parasitol. 107 191–205.PubMedCrossRefGoogle Scholar
  49. Tielens, A.G.M., and Van Hellemond, J., 1998, The electron transport chain in anaerobically functioning eukaryotes. Biochim. Biophys. Acta 1365 71–78.PubMedCrossRefGoogle Scholar
  50. Uyemura, S.A., Luo, S., Moreno, S.N.J., and Docampo, R., 2000, Oxidative phosphorylation, Ca2+ transport, and fatty acid-induced uncoupling in malaria parasites mitochondria. J. Biol. Chem. 275: 9709–9715.PubMedCrossRefGoogle Scholar
  51. Vaidya, A.B., 1998, Mitochondrial physiology as a target for atovaquone and other antimalarials. In Malaria (I.W. Sherman, ed.), ASM Press, Washington, D.C., pp. 673–675.Google Scholar
  52. Wallace, D.C., 1999, Mitochondrial diseases in man and mouse. Science, 283: 482–1488.CrossRefGoogle Scholar
  53. WHO, 1997, World malaria situation in 1994. Weekly Epidemiological Record, WHO.Google Scholar
  54. Wood, D., Darlison, M.G., Wilde, R.J., and Guest, J.R., 1984, Nucleotide sequence encoding the flavoprotein and hydrophobic subunits of the succinate dehydrogenase of Escherichia coli. Biochem. J. 222: 519–534.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Fumika Mi-Ichi
    • 1
  • Satoru Takeo
    • 1
  • Eizo Takashima
    • 1
  • Tamaki Kobayashi
    • 1
  • Hye-Sook Kim
    • 2
  • Yusuke Wataya
    • 2
  • Akira Matsuda
    • 3
  • Motomi Torii
    • 4
  • Takafumi Tsuboi
    • 4
  • Kiyoshi Kita
    • 1
  1. 1.Dept. of Biomedical Chemistry, Graduate School of MedicineThe University of TokyoHongo, Bunkyo-ku, TokyoJapan
  2. 2.Faculty of Pharmaceutical SciencesOkayama UniversityTsushima-naka, OkayamaJapan
  3. 3.Graduate School of Pharmaceutical ScienceHokkaido UniversitySapporoJapan
  4. 4.Dept. of Molecular parasitologyEhime University School of MedicineEhimeJapan

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