Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-27T15:18:24.527Z Has data issue: false hasContentIssue false
  • English
  • Français

The multiple roles of the mitochondrion of the malarial parasite

Published online by Cambridge University Press:  05 October 2004

J. KRUNGKRAI
J. KRUNGKRAI
Affiliation:
Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Rama 4 Road, Bangkok 10330, Thailand
Get access Rights & Permissions [Opens in a new window]

Abstract

Mitochondria of the malaria parasite Plasmodium falciparum are morphologically different between the asexual and sexual blood stages (gametocytes). In this paper recent findings of mitochondrial heterogeneity are reviewed based on their ultrastructural characteristics, metabolic activities and the differential expression of their genes in these 2 blood stages of the parasite. The existence of NADH dehydrogenase (complex I), succinate dehydrogenase (complex II), cytochrome c reductase (complex III) and cytochrome c oxidase (complex IV) suggests that the biochemically active electron transport system operates in this parasite. There is also an alternative electron transport branch pathway, including an anaerobic function of complex II. One of the functional roles of the mitochondrion in the parasite is the coordination of pyrimidine biosynthesis, the electron transport system and oxygen utilization via dihydroorotate dehydrogenase and coenzyme Q. Complete sets of genes encoding enzymes of the tricarboxylic acid cycle and the ATP synthase complex are predicted from P. falciparum genomics information. Other metabolic roles of this organelle include membrane potential maintenance, haem and coenzyme Q biosynthesis, and oxidative phosphorylation. Furthermore, the mitochondrion may be a chemotherapeutic target for antimalarial drug development. The antimalarial drug atovaquone targets the mitochondrion.

Keywords

malariamitochondrial metabolismelectron transport systemoxygen utilizationtricarboxylic acid cyclecoenzyme Q biosynthesis
Type
Review Article
Information
Parasitology , Volume 129 , Issue 5 , November 2004 , pp. 511 - 524
Copyright
© 2004 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

AIKAWA, M., HUFF, C. G. & SPRINZ, H. ( 1966). Comparative feeding mechanisms of avian and primate malarial parasites. Military Medicine 131, 969–983.CrossRefGoogle Scholar
AIKAWA, M. ( 1971). Plasmodium: the fine structure of malarial parasites. Experimental Parasitology 30, 284–320.CrossRefGoogle Scholar
ALANO, P. & CARTER, R. ( 1990). Sexual differentiation of malaria parasites. Annual Reviews of Microbiology 44, 429–449.CrossRefGoogle Scholar
BALDWIN, J., FARAJALLAH, A. M., MALMQUIST, N. A., RATHOD, P. K. & PHILLIPS, M. A. ( 2002). Malarial dihydroorotate dehydrogenase: substrate and inhibitor specificity. Journal of Biological Chemistry 277, 41827–41834.CrossRefGoogle Scholar
BASCO, L. K. & LE DRAS, J. ( 1994). In vitro activity of mitochondrial ATP synthetase inhibitors against Plasmodium falciparum. Journal of Eukaryotic Microbiology 41, 179–183.CrossRefGoogle Scholar
BENDER, A., VAN DOOREN, G., RALPH, S., McFADDEN, G. I. & SCHNEIDER, G. ( 2003). Properties and prediction of mitochondrial transit peptides from Plasmodium falciparum. Molecular and Biochemical Parasitology 132, 59–66.CrossRefGoogle Scholar
BRACCHI, V., LANGSLEY, G., THELU, J., ELING, W. & AMBROISE-THOMAS, P. ( 1996). PfKIN, an SNF1 type protein kinase of Plasmodium falciparum predominantly expressed in gametocytes. Molecular and Biochemical Parasitology 76, 299–303.CrossRefGoogle Scholar
CARTER, R., GRAVES, P. M., CREASEY, A., BYRNE, K., READ, D., ALANO, P. & FENTON, B. ( 1989). Plasmodium falciparum: an abundant stage-specific protein expressed during early gametocyte development. Experimental Parasitology 69, 140–149.CrossRefGoogle Scholar
CHAN, M. & SIM, T. S. ( 2003). Recombinant Plasmodium falciparum NADP-dependent isocitrate dehydrogenase is active and harbors a unique 26 amino acid tail. Experimental Parasitology 103, 120–126.CrossRefGoogle Scholar
CONWAY, D. J., FANELLO, C., LLOYD, J. M., AL-JOUBORI, B. M. A. S., BALOCH, A. H., SOMANATH, S. D., ROPER, C., ODUOLA, A. M. J., MULDER, B., POVOA, M. M., SINGH, B. & THOMAS, A. W. ( 2000). Origin of Plasmodium falciparum malaria is traced by mitochondrial DNA. Molecular and Biochemical Parasitology 111, 163–171.CrossRefGoogle Scholar
COWMAN, A., MORRY, M., BIGGS, B., CROSS, G. & FOOTE, S. ( 1988). Amino acid changes linked to pyrimethamine resistance in the dihydroorotate reductase-thymidylate synthase gene of Plasmodium falciparum. Proceedings of the National Academy of Sciences, USA 85, 9109–9113.CrossRefGoogle Scholar
CREASEY, A. M., RANFORD-CARTWRIGHT, L. C., MOORE, D. J., WILLIAMSON, D. H., WILSON, R. J. M., WALLIKER, D. & CARTER, R. ( 1993). Uniparental inheritance of the mitochondrial gene cytochrome b in Plasmodium falciparum. Current Genetics 23, 360–364.CrossRefGoogle Scholar
DE MACEDO, C. S., UHRIG, M. L., KIMURA, E. A. & KATZIN, A. M. ( 2002). Characterization of the isoprenoid chain of coenzyme Q in Plasmodium falciparum. FEMS Microbiology Letters 207, 13–20.CrossRefGoogle Scholar
DHANASEKARAN, S., CHANDRA, N. R., SAGAR, B. K. C., RANGARAJAN, P. N. & PADMANABAN, G. ( 2004). δ-aminolevulinic acid dehydratase from Plasmodium falciparum-indigenous vs imported. Journal of Biological Chemistry 279, 6934–6942.CrossRefGoogle Scholar
DILEEPAN, K. N. & KENNEDY, J. ( 1985). Complete inhibition of dihydroototate and superoxide production by 1,1,1-trifluoro-3-thenoylacetone in rat liver mitochondria. Biochemical Journal 225, 189–194.CrossRefGoogle Scholar
DIVO, A. A., GEARY, T. G., JENSEN, J. B. & GINSBURG, H. ( 1985). The mitochondrion of Plasmodium falciparum visualized by rhodamine 123 fluorescence. Journal of Protozoology 32, 442–446.CrossRefGoogle Scholar
DOERIG, C., DOERIG, C., HORROCKS, P., COYLE, J., CARTON, J., SULTAN, A., ARNOT, D. & CARTER, R. ( 1995). Pfcrk-1, a developmentally regulated cdc2-related protein kinase of Plasmodium falciparum. Molecular and Biochemical Parasitolgy 70, 167–174.CrossRefGoogle Scholar
DORIN, D., ALANO, P., BOCCACCIO, I., CICERON, L., DOERIG, C., SULPICE, R., PARZY, D. & DOERIG, C. ( 1999). An atypical mitogen-activated protein kinase (MAPK) homologue expressed in gametocytes of the human malaria parasite Plasmodium falciparum: identification of a MAPK significance. Journal of Biological Chemistry 274, 29912–29920.CrossRefGoogle Scholar
ECKSTEIN-LUDWIG, U., WEBB, R. J., VAN GOETHEM, I. D., EAST, J. M., LEE, A. G., KIMURA, M., O'NEILL, P. M., BRAY, P. G., WARD, S. A. & KRISHNA, S. ( 2003). Artemisinins target SERCA of Plasmodium falciparum. Nature, London 424, 957–961.CrossRefGoogle Scholar
ELLIS, J. E. ( 1994). Coenzyme Q homologs in parasitic protozoa as targets for chemotherapeutic attack. Parasitology Today 10, 296–301.CrossRefGoogle Scholar
ESCALANTE, A. A., FREELAND, D. E., COLLINS, W. E. & LAL, A. A. ( 1998). The evolution of primate malaria based on the gene encoding cytochrome b from the linear mitochondrial genome. Proceedings of the National Academy of Sciences, USA 95, 8124–8129.CrossRefGoogle Scholar
FANG, J. & BEATTIE, D. S. ( 2002). Novel FMN-containing rotenone-insensitive NADH dehydrogenase from Trypanosoma brucei mitochondria: isolation and characterization. Biochemistry 41, 3065–3072.CrossRefGoogle Scholar
FANG, J., ZHOU, H., RATHORE, D., SULLIVAN, M., SU, X. Z. & McCUTCHAN, T. F. ( 2004). Ambient glucose concentration and gene expression in Plasmodium falciparum. Molecular and Biochemical Parasitology 133, 125–129.CrossRefGoogle Scholar
FEAGIN, J. ( 1992). The 6-kb element of Plasmodium falciparum encodes mitochondrial cytochrome genes. Molecular and Biochemical Parasitolgy 52, 145–148.CrossRefGoogle Scholar
FEAGIN, J. & DREW, M. E. ( 1995). Plasmodium falciparum: alterations in organelle transcript abundance during the erythrocytic cycle. Experimental Parasitology 80, 430–440.CrossRefGoogle Scholar
FLECK, S. L., PUDNEY, M. & SINDEN, R. E. ( 1996). The effect of atovaquone (566C80) on the maturation and viability of Plasmodium falciparum gametocytes in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 90, 309–312.CrossRefGoogle Scholar
FRY, M. & BEESLEY, J. E. ( 1991). Mitochondria of mammalian Plasmodium spp. Parasitology 102, 17–26.CrossRefGoogle Scholar
FRY, M. & PUDNEY, M. ( 1992). Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4′-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80). Biochemical Pharmacology 43, 1545–1553.CrossRefGoogle Scholar
FUNES, S., DAVIDSON, E., REYES-PRIETO, A., MAGALLON, S., HERION, P., KING, M. P. & GONZALEZ-HALPHEN, D. ( 2002). A green algal apicoplast ancestor. Science 298, 2155.CrossRefGoogle Scholar
GARDNER, M. J., HALL, N., FUNG, E., WHITE, O., BERRIMAN, M., HYMAN, R. W., CARLTON, J. M., PAIN, A., NELSON, K. E., BOWMAN, S., PAULSEN, I. T., JAMES, K., EISEN, J. A., RUTHERFORD, K., SALZBERG, S. L., CRAIG, A., KYES, S., CHAN, M., NENE, V., SHALLOM, S. J., SUH, B., PETERSON, J., ANGIUOLI, S., PERTEA, M., ALLEN, J., SELENGUT, J., HAFT, D., MATHER, M. W., VAIDYA, A. B., MARTIN, D. M. A., FAIRLAMB, A. H., FRAUNHOLZ, M. J., ROOS, D. S., RALPH, S. A., McFADDEN, G. I., CUMMINGS, L. M., SUBRAMANIAN, G. M., MUNGALL, C., VENTER, J. C., CARUCCI, D. J., HOFFMAN, S. L., NEWBOLD, C., DAVIS, R. W., FRASER, C. M. & BARRELL, B. ( 2002). Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, London 419, 498–511.CrossRefGoogle Scholar
GINSBURG, H., DIVO, A. A., GEARY, T. G., BOLAND, M. T. & JENSEN, J. B. ( 1986). Effect of mitochondrial inhibitors on intraerythrocytic Plasmodium falciparum in in vitro cultures. Journal of Protozoology 33, 121–125.CrossRefGoogle Scholar
GUERIN, P. J., OLLIARO, P., NOSTEN, F., DRUILHE, P., LAXMINARAYAN, R., BINKA, F., KILAMA, W. L., FORD, N. & WHITE, N. J. ( 2002). Malaria: current status of control, diagnosis, treatment, and a proposed agenda of research and development. Lancet Infectious Diseases 2, 564–573.CrossRefGoogle Scholar
GUTTERIDGE, W. E., DAVE, D. & RICHARDS, W. H. G. ( 1979). Conversion of dihydroorotate to orotate in parasitic protozoa. Biochimica et Biophysica Acta 582, 390–401.CrossRefGoogle Scholar
HATEFI, Y. ( 1985). The mitochondrial electron transport and oxidative phosphorylation system. Annual Reviews of Biochemistry 54, 1015–1069.CrossRefGoogle Scholar
HORROCKS, P., DECHERING, K. & LANZER, M. ( 1998). Control of gene expression in Plasmodium falciparum. Molecular and Biochemical Parasitolgy 95, 171–181.CrossRefGoogle Scholar
HUDSON, A. T. ( 1984). Lapinone, menoctone, hydroxyquinolinequinones and similar structures. In Antimalarial Drugs II, Handbook of Experimental Pharmacology (ed. Peters, W. & Richards, W. H. G.), pp. 343–361. Springer-Verlag, New York.CrossRef
HUDSON, A. T., RANDALL, A. W., FRY, M., GINGER, C. D., HILL, B., LATTER, V. S., McHARDY, N. & WILLIAMS, R. B. ( 1985). Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum antiprotozoal activity. Parasitology 90, 45–55.CrossRefGoogle Scholar
IFEDIBA, T. & VANDERBERG, J. P. ( 1981). Complete in vitro maturation of Plasmodium falciparum gametocytes. Nature, London 294, 364–366.CrossRefGoogle Scholar
JOSEPH, J. T., ALDRITT, S. M., UNNASCH, T., PUIJALON, O. & WIRTH, D. F. ( 1989). Characterization of a conserved extrachromosomal element isolated from the avian malarial parasite Plasmodium gallinaceum. Molecular Cell Biology 9, 3621–3629.CrossRefGoogle Scholar
KANESHIRO, E. S., SUL, D. & HAZRA, B. ( 2000). Effects of atovaquone and diospyrin-based drugs on ubiquinone biosynthesis in Pneumocystis carinii organisms. Antimicrobial Agents and Chemotherapy 44, 14–18.CrossRefGoogle Scholar
KAWAI, S., KANO, S. & SUZUKI, M. ( 1993). Morphologic effects of artemether on Plasmodium falciparum in Aotus Trivirgatus. American Journal of Tropical Medicine and Hygiene 49, 812–818.CrossRefGoogle Scholar
KESSL, J. J., LANGE, B. B., MERBITZ-ZAHRADNIK, T., ZWICKER, K., HILL, P., MEUNIER, R., HUNTE, C., MESHNICK, S. & TRUMPOWER, B. L. ( 2003). Molecular basis for atovaquone binding to the cytochrome bc1 complex. Journal of Biological Chemistry 278, 31312–31318.CrossRefGoogle Scholar
KITA, K., HIRAWAKE, H., MIYADERA, H., AMINO, H. & TAKEO, S. ( 2002). Role of complex II in anaerobic respiration of the parasite mitochondria from Ascaris suum and Plasmodium falciparum. Biochimica et Biophysica Acta 1553, 123–139.CrossRefGoogle Scholar
KRUNGKRAI, J. ( 1991). Malarial dihydroorotate dehydrogenase mediates superoxide radical production. Biochemistry International 24, 833–839.Google Scholar
KRUNGKRAI, J. ( 1993 a). Dihydroorotase and dihydroorotate dehydrogenase as a target for antimalarial drugs. Drugs of the Future 18, 441–450.Google Scholar
KRUNGKRAI, J. ( 1993 b). A novel form of orotate reductase that converts orotate to dihydroorotate in Plasmodium falciparum and Plasmodium berghei. Comparative Biochemistry and Physiology 104B, 267–274.Google Scholar
KRUNGKRAI, J. ( 1995). Purification, characterization and localization of mitochondrial dihydroorotate dehydrogenase in Plasmodium falciparum, human malaria parasite. Biochimica et Biophysica Acta 1243, 351–360.CrossRefGoogle Scholar
KRUNGKRAI, J. ( 2000). Structure and function of mitochondria in human malarial pathogen Plasmodium falciparum. Trends in Comparative Biochemistry & Physiology 6, 95–107.Google Scholar
KRUNGKRAI, J., BURAT, D., KUDAN, S., KRUNGKRAI, S. R. & PRAPUNWATTANA, P. ( 1999 b). Mitochondrial oxygen consumption in asexual and sexual blood stages of the human malarial parasite, Plasmodium falciparum. Southeast Asian Journal of Tropical Medicine and Public Health 30, 636–642.Google Scholar
KRUNGKRAI, J., CERAMI, A. & HENDERSON, G. B. ( 1990). Pyrimidine biosynthesis in parasitic protozoa: purification of a monofunctional dihydroorotase from Plasmodium berghei and Crithidia fasciculata. Biochemistry 29, 6270–6275.CrossRefGoogle Scholar
KRUNGKRAI, J., CERAMI, A. & HENDERSON, G. B. ( 1991). Purification and characterization of dihydroorotate dehydrogenase from the rodent malaria parasite Plasmodium berghei. Biochemistry 30, 1934–1939.CrossRefGoogle Scholar
KRUNGKRAI, J., KANCHANARITHISAK, R., KRUNGKRAI, S. R. & ROCHANAKIJ, S. ( 2002). Mitochondrial NADH dehydrogenase from Plasmodium falciparum and Plasmodium berghei. Experimental Parasitology 100, 54–61.CrossRefGoogle Scholar
KRUNGKRAI, J., KRUNGKRAI, S. R. & BHUMIRATANA, A. ( 1993). Plasmodium berghei: partial purification and characterization of the mitochondrial cytochrome c oxidase. Experimental Parasitology 77, 136–146.CrossRefGoogle Scholar
KRUNGKRAI, J., KRUNGKRAI, S. R. & PHAKANONT, K. ( 1992). Antimalarial activity of orotate analogs that inhibit dihydroorotase and dihydroorotate dehydrogenase. Biochemical Pharmacology 43, 1295–1301.CrossRefGoogle Scholar
KRUNGKRAI, J., KRUNGKRAI, S. R., SURAVERATUM, N. & PRAPUNWATTANA, P. ( 1997). Mitochondrial ubiquinol-cytochrome c reductase and cytochrome c oxidase: chemotherapeutic targets in malarial parasites. Biochemistry and Molecular Biology International 42, 1007–1014.CrossRefGoogle Scholar
KRUNGKRAI, J., KRUNGKRAI, S. R., SURAVERATUM, N. & PRAPUNWATTANA, P. ( 1998). Mitochondrial ubiquinol-cytochrome c reductase: a chemotherapeutic target in human malarial parasites. In Proceedings of International Congress of Parasitology IX (ed. Tada, I., Kojima, S. & Tsuji, M.), pp. 949–952. Bologna, Monduzzi Editore.CrossRef
KRUNGKRAI, S. R., LEARNGARAMKUL, P., KUDAN, S., PRAPUNWATTANA, P. & KRUNGKRAI, J. ( 1999 a). Mitochondrial heterogeneity in human malarial parasite Plasmodium falciparum. Science Asia 25, 77–83.Google Scholar
KRUNGKRAI, J., PRAPUNWATTANA, P. & KRUNGKRAI, S. R. ( 2000). Ultrastructure and function of mitochondria in gametocytic stage of Plasmodium falciparum. Parasite 7, 19–26.CrossRefGoogle Scholar
KRUNGKRAI, J., PRAPUNWATTANA, P., WICHITKUL, C., REUNGPRAPAVUT, S., KRUNGKRAI, S. R. & HORII, T. ( 2003). Molecular biology and biochemistry of malarial parasite pyrimidine biosynthetic pathway. Southeast Asian Journal of Tropical Medicine & Public Health 34 (Suppl. 2), 32–42.Google Scholar
LANGRETH, S. G., JENSEN, J. B., REESE, R. T. & TRAGER, W. ( 1978). Fine structure of human malaria in vitro. Journal of Protozoology 25, 443–452.CrossRefGoogle Scholar
LANNERS, H. N. ( 1991). Effect of the 8-aminoquinoline primaquine on culture-derived gametocytes of the malaria parasite Plasmodium falciparum. Parasitology Research 77, 478–481.CrossRefGoogle Scholar
LEARNGARAMKUL, P., PETMITR, S., KRUNGKRAI, S. R., PRAPUNWATTANA, P. & KRUNGKRAI, J. ( 1999). Molecular characterization of mitochondria in asexual and sexual blood stages of Plasmodium falciparum. Molecular Cell Biology Research Communications 2, 15–20.CrossRefGoogle Scholar
LI, J. L. & BAKER, D. A. ( 1998). A putative protein serine/threonine phosphatase from Plasmodium falciparum contains a large N-terminal extension and five unique inserts in the catalytic domain. Molecular and Biochemical Parasitolgy 95, 287–295.CrossRefGoogle Scholar
LIKHITWITAYAWUID, K., KAEWAMATAWONG, R., RUANGRUNGSI, N. & KRUNGKRAI, J. ( 1998). Antimalarial naphthoquinones from Nepenthes thorelii. Planta Medica 64, 237–241.CrossRefGoogle Scholar
LOBO, C. A. & KUMAR, N. ( 1998). Sexual differentiation and development in the malaria parasite. Parasitology Today 14, 146–150.CrossRefGoogle Scholar
LUTTIK, M. A. H., OVERKAMP, K. M., KOTTER, P., DE VRIES, S., VAN DIJKEN, J. P. & PRONK, J. T. ( 1998). The Saccharomyces cerevisiae NDE1 and NDE2 genes encode separate mitochondrial NADH dehydrogenase catalyzing the oxidation of cytosolic NADH. Journal of Biological Chemistry 273, 24529–24534.CrossRefGoogle Scholar
McINTOSH, M. T., SRIVASTAVA, R. & VAIDYA, A. B. ( 1998). Divergent evolutionary constraints on mitochondrial and nuclear genomes of malaria parasites. Molecular and Biochemical Parasitolgy 95, 69–80.CrossRefGoogle Scholar
MURPHY, A. D., DOELLER, J. E., HEARN, B. & LANG-UNNASCH, N. ( 1997). Plasmodium falciparum: cyanide-resistant oxygen consumption. Experimental Parasitology 87, 112–120.CrossRefGoogle Scholar
NAGLEY, P. ( 1991). Coordination of gene expression in the formation of mammalian mitochondria. Trends in Genetics 7, 1–4.CrossRefGoogle Scholar
PEREZ-MARTINEZ, X., ANTARAMIAN, A., VAZQUEZ-ACEVEDO, M., FUNES, S., TOLKUNOVA, E., D'ALAYER, J., CLAROS, M. G., DAVIDSON, E., KING, M. P. & GONZALEZ-HALPHEN, D. ( 2001). Subunit II of cytochrome c oxidase in Chlamydomonad algae is a heterodimer encoded by two independent nuclear genes. Journal of Biological Chemistry 276, 11302–11309.CrossRefGoogle Scholar
PETERS, J. M., CHEN, N., GATTON, M., KORSINCZKY, M., FOWLER, E. V., SAUL, A. & CHENG, Q. ( 2002). Mutations in cytochrome b resulting in atovaquone resistance are associated with loss of fitness in Plasmodium falciparum. Antimicrobial Agents & Chemotherapy 46, 2435–2441.CrossRefGoogle Scholar
PETMITR, S. & KRUNGKRAI, J. ( 1995). Mitochondrial cytochrome b gene in two developmental stages of human malarial parasite Plasmodium falciparum. Southeast Asian Journal of Tropical Medicine and Public Health 26, 600–605.Google Scholar
PORTER, T. H. & FOLKERS, K. ( 1974). Antimetabolites of coenzyme Q. Their potential application as antimalarials. Angewandte Chemie International Edition in English 13, 559–618.Google Scholar
PRAPUNWATTANA, P., O'SULLIVAN, W. J. & YUTHAVONG, Y. ( 1988). Depression of Plasmodium falciparum dihydroorotate dehydrogenase activity in in vitro culture by tetracycline. Molecular and Biochemical Parasitology 27, 119–124.CrossRefGoogle Scholar
PREISER, P. R., WILSON, R. J., MOORE, P. W., McCREADY, S., HAJIBAGHERI, M. A., BLIGHT, K. J., STRATH, M. & WILLIAMSON, D. H. ( 1996). Recombination associated with replication of malarial mitochondrial DNA. EMBO Journal 15, 684–693.Google Scholar
RAWLINGS, D. J., FUJIOKA, H., FRIED, M., KEISTER, D. B., AIKAWA, M. & KASLOW, D. C. ( 1992). Alpha-tubulin II is a male-specific protein in Plasmodium falciparum. Molecular and Biochemical Parasitology 56, 239–250.CrossRefGoogle Scholar
RIDLEY, R. G. ( 2002). Medical need, scientific opportunity and the drive for antimalarial drugs. Nature, London 415, 686–693.CrossRefGoogle Scholar
SATO, S., RANGACHARI, K. & WILSON, R. J. M. ( 2003). Targeting GFP to the malarial mitochondrion. Molecular and Biochemical Parasitology 130, 155–158.CrossRefGoogle Scholar
SATO, S. & WILSON, R. J. M. ( 2004). The use of DsRED in single- and dual-color fluorescence labeling of mitochondrial and plastid organelles in Plasmodium falciparum. Molecular and Biochemical Parasitology 134, 175–179.CrossRefGoogle Scholar
SCHEIBEL, L. W. ( 1988). Plasmodial metabolism: Carbohydrate. In Malaria, Vol. I (ed. Wernsdorfer, W. H. & McGregor, I.), pp. 171–217. Churchill Livingstone, New York.
SCHEIBEL, L. W., ASHTON, H. S. & TRAGER, W. ( 1979). Plasmodium falciparum: microaerophillic requirements in human red blood cells. Experimental Parasitology 47, 410–418.CrossRefGoogle Scholar
SHERMAN, I. W. ( 1979). Biochemistry of Plasmodium (malaria parasites). Microbiological Reviews 43, 453–495.Google Scholar
SIDDALL, M. E. & DESSER, S. S. ( 1992). Ultrastructure of gametogenesis and sporogony of Haemogregarina (sensu lato) myoxocephali (Apicomplexa: Adeleina) in the marine leech Malmiana scorpii. Journal of Protozoology 39, 545–554.CrossRefGoogle Scholar
SINDEN, R. E. & SMALLEY, M. E. ( 1979). Gametocytogenesis of Plasmodium falciparum in vitro: the cell-cycle. Parasitology 79, 277–296.CrossRefGoogle Scholar
SINDEN, R. E. ( 1982). Gametocytogenesis of Plasmodium falciparum in vitro: an electron microscopic study. Parasitology 84, 1–11.CrossRefGoogle Scholar
SINDEN, R. E. ( 1983). Sexual development of malarial parasites. Advances in Parasitology 22, 154–216.CrossRefGoogle Scholar
SRIVASTAVA, I. K., MORRISEY, J. M., DARROUZET, E., DALDAL, F. & VAIDYA, A. B. ( 1999). Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. Molecular Microbiology 33, 704–711.CrossRefGoogle Scholar
SRIVASTAVA, I. K., ROTTENBERG, H. & VAIDYA, A. B. ( 1997). Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite. Journal of Biological Chemistry 272, 3961–3966.CrossRefGoogle Scholar
SURAVERATUM, N., KRUNGKRAI, S. R., LEARNGARAMKUL, P., PRAPUNWATTANA, P. & KRUNGKRAI, J. ( 2000). Purification and characterization of Plasmodium falciparum succinate dehydrogenase. Molecular and Biochemical Parasitology 105, 215–222.CrossRefGoogle Scholar
SUZUKI, T., HASHIMOTO, T., YABU, Y., KIDO, Y., SAKAMOTO, K., NIHEI, C., HATO, M., SUZUKI, S., AMANO, Y., NAGAI, K., HOSOKAWA, T., MINAGAWA, N., OHTA, N. & KITA, K. ( 2004). Direct evidence for cyanide-insensitive quinol oxidase (alternative oxidase) in apicomplexan parasite Cryptosporidium parvum: phylogenetic and therapeutic implications. Biochemical and Biophysical Research Communications 313, 1044–1052.CrossRefGoogle Scholar
TAKASHIMA, E., TAKAMIYA, S., TAKEO, S., MI-ICHI, F., AMINO, H. & KITA, K. ( 2001). Isolation of mitochondria from Plasmodium falciparum showing dihydroorotate dependent respiration. Parasitology International 50, 273–278.CrossRefGoogle Scholar
TAKEO, S., KOKAZE, A., NG, C. S., MIZUCHI, D., WATANABE, J., TANABE, K., KOJIMA, S. & 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. Molecular and Biochemical Parasitology 107, 191–205.CrossRefGoogle Scholar
TRAGER, W. & JENSEN, J. B. ( 1976). Human malaria in continuous culture. Science 193, 673–677.CrossRefGoogle Scholar
TROPICAL DISEASE RESEARCH ( 1997). Thirteenth Programme Report: Progress 1995–1996. Geneva, World Health Organization.
UYEMURA, S. A., LUO, S., MORENO, S. N. J. & DOCAMPO, R. ( 2000). Oxidative phosphorylation, Ca2+ transport, and fatty acid-induced uncoupling in malaria parasites mitochondria. Journal of Biological Chemistry 275, 9709–9715.CrossRefGoogle Scholar
UYEMURA, S. A., LUO, S., VIEIRA, M., MORENO, S. N. & DOCAMPO, R. ( 2004). Oxidative phosphorylation and rotenone-insensitive malate- and NADH-quinone oxidoreductases in Plasmodium yoelii yoelii mitochondria in situ. Journal of Biological Chemistry 279, 385–393.CrossRefGoogle Scholar
VAIDYA, A. B., LASHGARI, M. S., POLOGE, L. G. & MORRISEY, J. ( 1993). Structural features of Plasmodium cytochrome b that may underline susceptibility to 8-aminoquinolines and hydroxynaphthoquinones. Molecular and Biochemical Parasitology 58, 33–42.CrossRefGoogle Scholar
VARADHARAJAN, S., DHANASEKARAN, S., BONDAY, Z. Q., RANGARAJAN, P. N. & PADMANABAN, G. ( 2002). Involvement of δ-aminolaevulinate synthase encoded by the parasite gene in de novo haem synthesis by Plasmodium falciparum. Biochemical Journal 367, 321–327.CrossRefGoogle Scholar
WAN, Y. P., PORTER, T. H. & FOLKERS, K. ( 1974). Antimalarial quinones for prophylaxis based on a rationale of inhibition of electron transfer in Plasmodium. Proceedings of the National Academy of Sciences, USA 71, 952–956.CrossRefGoogle Scholar
WATERS, A. P., SYIN, C. & McCUTCHAN, T. F. ( 1989). Developmental regulation of stage-specific ribosome populations in Plasmodium. Nature, London 342, 438–440.CrossRefGoogle Scholar
WATERS, A. P., VAN SPAENDONK, R. M., RAMESAR, J., VERVENNE, R. A., DIRKS, R. W., THOMPSON, J. & JANSE, C. J. ( 1997). Species-specific regulation and switching of transcription between stage-specific ribosomal RNA genes in Plasmodium berghei. Journal of Biological Chemistry 272, 3583–3589.CrossRefGoogle Scholar
WESSELING, J. G., DIRKS, R., SMITS, M. A. & SCHOENMAKERS, J. G. G. ( 1989). Nucleotide sequence and expression of a beta-tubulin gene from Plasmodium falciparum. Gene 83, 301–309.CrossRefGoogle Scholar
WIESNER, R. J. ( 1992). Direct quantification of picomolar concentrations of mRNAs by mathematical analysis of a reverse transcription/exponential polymerase chain reaction assay. Nucleic Acids Research 20, 5863–5864.CrossRefGoogle Scholar
WILSON, C. M., SMITH, A. B. & BAYLON, R. V. ( 1996). Characterization of δ-aminolevulinate synthase gene homologue in P. falciparum. Molecular and Biochemical Parasitology 79, 135–140.CrossRefGoogle Scholar
WRENGER, C. & MULLER, S. ( 2003). Isocitrate dehydrogenase of Plasmodium falciparum. European Journal of Biochemistry 270, 1775–1783.CrossRefGoogle Scholar
ZHAO, Y., HANTON, W. K. & LEE, K. H. ( 1986). Antimalarial agents, 2. Artesunate, an inhibitor of cytochrome oxidase activity in Plasmodium berghei. Journal of Natural Products 49, 139–142.Google Scholar