Skip to main content
SpringerLink
Log in

A Post-genomic View of the Mitochondrion in Malaria Parasites

  • Chapter
Malaria: Drugs, Disease and Post-genomic Biology

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 295))

Abstract

Mitochondria in Plasmodium parasites have many characteristics that distinguish them from mammalian mitochondria. Selective targeting of malaria parasite mitochondrial physiology has been exploited in successful antimalarial chemotherapy. At present, our understanding of the functions served by the parasite mitochondrion is somewhat limited, but the availability of the genomic sequences makes it possible to develop a framework of possible mitochondrial functions by providing information on genes encoding mitochondrially targeted proteins. This review aims to provide an overview of mitochondrial physiology in this post-genomic era. Although in many cases direct experimental proof for their mitochondrial functionsmay not be available at present, descriptions of these potential mitochondrial proteins can provide a basis for experimental approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abrahamsen MS, Templeton TJ, Enomoto S, Abrahante JE, Zhu G, Lancto CA, Deng M, Liu C, Widmer G, Tzipori S, Buck GA, Xu P, Bankier AT, Dear PH, Konfortov BA, Spriggs HF, Iyer L, Anantharaman V, Aravind L, Kapur V (2004) Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science 304:441–445

    Article  PubMed  CAS  Google Scholar 

  • Aikawa M (1971) Parasitological review. Plasmodium: the fine structure of malarial parasites. Exp Parasitol 30:284–320

    Article  PubMed  CAS  Google Scholar 

  • Baldwin J, Farajallah AM, Malmquist NA, Rathod PK, Phillips MA (2002) Malarial dihydroorotate dehydrogenase. Substrate and inhibitor specificity. J Biol Chem 277:41827–41834

    PubMed  CAS  Google Scholar 

  • Beinert H (2000) Iron-sulfur proteins: ancient structures, still full of surprises. J Biol Inorg Chem 5:2–15

    PubMed  CAS  Google Scholar 

  • Bender A, van Dooren GG, Ralph SA, McFadden GI, Schneider G (2003) Properties and prediction of mitochondrial transit peptides from Plasmodium falciparum. Mol Biochem Parasitol 132:59–66

    Article  PubMed  CAS  Google Scholar 

  • Boyer PD (2001) New insights into one of nature’s remarkable catalysts, the ATP synthase. Mol Cell 8:246–247

    Article  PubMed  CAS  Google Scholar 

  • Brumme S, Kruft V, Schmitz UK, Braun HP (1998) New insights into the co-evolution of cytochrome c reductase and the mitochondrial processing peptidase. J Biol Chem 273:13143–13149

    Article  PubMed  CAS  Google Scholar 

  • Carlton JM, Angiuoli SV, Suh BB, Kooij TW, Pertea M, Silva JC, Ermolaeva MD, Allen JE, Selengut JD, Koo HL, Peterson JD, Pop M, Kosack DS, Shumway MF, Bidwell SL, Shallom SJ, van Aken SE, Riedmuller SB, Feldblyum TV, Cho JK, Quackenbush J, Sedegah M, Shoaibi A, Cummings LM, Florens L, Yates JR, Raine JD, Sinden RE, Harris MA, Cunningham DA, Preiser PR, Bergman LW, Vaidya AB, van Lin LH, Janse CJ, Waters AP, Smith HO, White OR, Salzberg SL, Venter JC, Fraser CM, Hoffman SL, Gardner MJ, Carucci DJ (2002) Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature 419:512–519

    Article  PubMed  CAS  Google Scholar 

  • Chan M, Sim TS (2003) Recombinant Plasmodium falciparum NADP-dependent isocitrate dehydrogenase is active and harbours a unique 26 amino acid tail. Exp Parasitol 103:120–126

    Article  PubMed  CAS  Google Scholar 

  • Claros MG, Vincens P (1996) Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur J Biochem 241:779–786

    Article  PubMed  CAS  Google Scholar 

  • Dhanasekaran S, Chandra NR, Chandrasekhar Sagar BK, Rangarajan PN, Padmanaban G (2004) Delta-aminolevulinic acid dehydratase from Plasmodium falciparum: indigenous versus imported. J Biol Chem 279:6934–6942

    Article  PubMed  CAS  Google Scholar 

  • Ellis KE, Clough B, Saldanha JW, Wilson RJ (2001) Nifs and Sufs in malaria. Mol Microbiol 41:973–981

    Article  PubMed  CAS  Google Scholar 

  • Feagin JE, Werner E, Gardner MJ, Williamson DH, Wilson RJ (1992) Homologies between the contiguous and fragmented rRNAs of the two Plasmodium falciparum extrachromosomal DNAs are limited to core sequences. Nucleic Acids Res 20:879–887

    PubMed  CAS  Google Scholar 

  • Foth BJ, McFadden GI (2003) The apicoplast: a plastid in Plasmodium falciparum and other Apicomplexan parasites. Int Rev Cytol 224:57–110

    PubMed  Google 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). Biochem Pharmacol 43:1545–1553

    Article  PubMed  CAS  Google Scholar 

  • Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM, Fairlamb AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM, Subramanian GM, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW, Fraser CM, Barrell B (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419:498–511

    PubMed  CAS  Google Scholar 

  • Gutteridge WE, Dave D, Richards WH (1979) Conversion of dihydroorotate to orotate in parasitic protozoa. Biochim Biophys Acta 582:390–401

    PubMed  CAS  Google Scholar 

  • Ji YE, Mericle BL, Rehkopf DH, Anderson JD, Feagin JE (1996) The Plasmodium falciparum 6 kb element is polycistronically transcribed. Mol Biochem Parasitol 81:211–223

    Article  PubMed  Google Scholar 

  • Joy DA, Feng X, Mu J, Furuya T, Chotivanich K, Krettli AU, Ho M, Wang A, White NJ, Suh E, Beerli P, Su XZ (2003) Early origin and recent expansion of Plasmodium falciparum. Science 300:318–321

    Article  PubMed  CAS  Google Scholar 

  • LaGier MJ, Tachezy J, Stejskal F, Kutisova K, Keithly JS (2003) Mitochondrial-type iron-sulfur cluster biosynthesis genes (IscS and IscU) in the apicomplexan Cryptosporidium parvum. Microbiology 149:3519–3530

    Article  PubMed  CAS  Google Scholar 

  • Lang-Unnasch N (1995) Plasmodium falciparum: antiserum to malate dehydrogenase. Exp Parasitol 80:357–359

    PubMed  CAS  Google Scholar 

  • Li J, Maga JA, Cermakian N, Cedergren R, Feagin JE (2001) Identification and characterization of a Plasmodium falciparum RNA polymerase gene with similarity to mitochondrial RNA polymerases. Mol Biochem Parasitol 113:261–269

    Article  PubMed  CAS  Google Scholar 

  • Lill R, Kispal G (2000) Maturation of cellular Fe-S proteins: an essential function of mitochondria. Trends Biochem Sci 25:352–356

    Article  PubMed  CAS  Google Scholar 

  • Loyevsky M, LaVaute T, Allerson CR, Stearman R, Kassim OO, Cooperman S, Gordeuk VR, Rouault TA (2001) An IRP-like protein from Plasmodium falciparum binds to a mammalian iron-responsive element. Blood 98:2555–2562

    Article  PubMed  CAS  Google Scholar 

  • Luttik MA, Overkamp KM, Kotter P, de Vries S, van Dijken JP, Pronk JT (1998) The Saccharomyces cerevisiae NDE1 and NDE2 genes encode separate mitochondrial NADH dehydrogenases catalyzing the oxidation of cytosolic NADH. J Biol Chem 273:24529–24534

    Article  PubMed  CAS  Google Scholar 

  • McIntosh MT, Srivastava R, Vaidya AB (1998) Divergent evolutionary constraints on mitochondrial and nuclear genomes of malaria parasites. Mol Biochem Parasitol 95:69–80

    Article  PubMed  CAS  Google Scholar 

  • Perez-Martinez X, Antaramian A, Vazquez-Acevedo M, Funes S, Tolkunova E, d’Alayer J, Claros MG, Davidson E, King MP, Gonzalez-Halphen D (2001) Subunit II of cytochrome c oxidase in Chlamydomonad algae is a heterodimer encoded by two independent nuclear genes. J Biol Chem 276:11302–11309

    Article  PubMed  CAS  Google Scholar 

  • Preiser PR, Wilson RJ, Moore PW, McCready S, Hajibagheri MA, Blight KJ, Strath M, Williamson DH (1996) Recombination associated with replication of malarial mitochondrial DNA. EMBO J 15:684–693

    PubMed  CAS  Google Scholar 

  • Ralph SA, Van Dooren GG, Waller RF, Crawford MJ, Fraunholz MJ, Foth BJ, Tonkin CJ, Roos DS, McFadden GI (2004) Tropical infectious diseases: Metabolic maps and functions of the Plasmodium falciparum apicoplast. Nat RevMicrobiol 2:203–216

    CAS  Google Scholar 

  • Riordan CE, Ault JG, Langreth SG, Keithly JS (2003) Cryptosporidium parvum Cpn60 targets a relict organelle. Curr Genet 44:138–147

    Article  PubMed  CAS  Google Scholar 

  • Roberts CW, Roberts F, Henriquez FL, Akiyoshi D, Samuel BU, Richards TA, Milhous W, Kyle D, McIntosh L, Hill GC, Chaudhuri M, Tzipori S, McLeod R (2004) Evidence for mitochondrial-derived alternative oxidase in the apicomplexan parasite Cryptosporidium parvum: a potential anti-microbial agent target. Int J Parasitol 34:297–308

    PubMed  CAS  Google Scholar 

  • Sato S, Clough B, Coates L, Wilson RJ (2004) Enzymes for heme biosynthesis are found in both the mitochondrion and plastid of themalaria parasite Plasmodium falciparum. Protist 155:117–125

    Article  PubMed  CAS  Google Scholar 

  • Sato S, Rangachari K, Wilson RJ (2003) Targeting GFP to themalarial mitochondrion. Mol Biochem Parasitol 130:155–158

    Article  PubMed  CAS  Google Scholar 

  • Seeber F (2002) Biogenesis of iron-sulphur clusters in amitochondriate and apicomplexan protists. Int J Parasitol 32:1207–1217

    PubMed  CAS  Google Scholar 

  • Sickmann A, Reinders J, Wagner Y, Joppich C, Zahedi R, Meyer HE, Schonfisch B, Perschil I, Chacinska A, Guiard B, Rehling P, Pfanner N, Meisinger C (2003) The proteome of Saccharomyces cerevisiae mitochondria. Proc Natl Acad Sci USA 100:13207–13212

    Article  PubMed  CAS  Google Scholar 

  • Srivastava IK, Morrisey JM, Darrouzet E, Daldal F, Vaidya AB (1999) Resistance mutations reveal the atovaquone-binding domain of cytochrome b inmalaria parasites. Mol Microbiol 33:704–711

    Article  PubMed  CAS  Google Scholar 

  • Srivastava IK, Rottenberg H, Vaidya AB (1997) Atovaquone, a broad spectrumantiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite. J Biol Chem 272:3961–3966

    Article  PubMed  CAS  Google Scholar 

  • Suplick K, Morrisey J, Vaidya AB (1990) Complex transcription from the extrachromosomal DNA encoding mitochondrial functions of Plasmodiumyoelii. Mol Cell Biol 10:6381–6388

    PubMed  CAS  Google Scholar 

  • Suraveratum N, Krungkrai SR, Leangaramgul P, Prapunwattana P, Krungkrai J (2000) Purification and characterization of Plasmodium falciparum succinate dehydrogenase. Mol Biochem Parasitol 105:215–222

    Article  PubMed  CAS  Google Scholar 

  • Takeo S, Kokaze A, Ng CS, Mizuchi D, Watanabe JI, 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. Mol Biochem Parasitol 107:191–205

    Article  PubMed  CAS  Google Scholar 

  • Tonkin CJ, van Dooren GG, Spurck TP, Struck NS, Good RT, Handman E, Cowman AF, McFadden GI (2004) Localization of organellar proteins in Plasmodium falciparum using a novel set of transfection vectors and a new immunofluorescence fixation method. Mol Biochem Parasitol 137:13–21

    Article  PubMed  CAS  Google Scholar 

  • Vaidya AB (1998) Mitochondrial physiology as a target for atovaquone and other antimalarials. In: Sherman IW (ed.) Malaria: Parasite biology, pathogenesis, and protection. ASM Press, Washington DC, pp 355–368

    Google Scholar 

  • Vaidya AB (2004) Mitochondrial and plastid functions as antimalarial drug targets. Curr Drug Targets Infect Disord 4:11–23

    Article  PubMed  CAS  Google Scholar 

  • Vaidya AB, Akella R, Suplick K (1989) Sequences similar to genes for two mitochondrial proteins and portions of ribosomal RNA in tandemly arrayed 6-kilobase-pair DNA of a malarial parasite. Mol Biochem Parasitol 35:97–107

    Article  PubMed  CAS  Google Scholar 

  • Vaidya AB, Arasu P (1987) Tandemly arranged gene clusters of malarial parasites that are highly conserved and transcribed. Mol Biochem Parasitol 22:249–257

    Article  PubMed  CAS  Google Scholar 

  • Vaidya AB, Lashgari MS, Pologe LG, Morrisey J (1993a) Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones. Mol Biochem Parasitol 58:33–42

    Article  PubMed  CAS  Google Scholar 

  • Vaidya AB, Morrisey J, Plowe CV, Kaslow DC, Wellems TE (1993b) Unidirectional dominance of cytoplasmic inheritance in two genetic crosses of Plasmodium falciparum. Mol Cell Biol 13:7349–7357

    PubMed  CAS  Google Scholar 

  • Varadharajan S, Sagar BK, Rangarajan PN, Padmanaban G (2004) Localization of ferrochelatase in Plasmodium falciparum. Biochem J 384:429–436

    PubMed  CAS  Google Scholar 

  • Wilson RJ (2002) Progress with parasite plastids. J Mol Biol 319:257–274

    PubMed  CAS  Google Scholar 

  • Wilson RJ, Denny PW, Preiser PR, Rangachari K, Roberts K, Roy A, Whyte A, Strath M, Moore DJ, Moore PW, Williamson DH (1996) Complete gene map of the plastidlike DNA of the malaria parasite Plasmodium falciparum. J Mol Biol 261:155–172

    PubMed  CAS  Google Scholar 

  • Wrenger C, Muller S (2003) Isocitrate dehydrogenase of Plasmodium falciparum. Eur J Biochem 270:1775–1783

    Article  PubMed  CAS  Google Scholar 

  • Xu P, Widmer G, Wang Y, Ozaki LS, Alves JM, Serrano MG, Puiu D, Manque P, Akiyoshi D, Mackey AJ, Pearson WR, Dear PH, Bankier AT, Peterson DL, Abrahamsen MS, Kapur V, Tzipori S, Buck GA (2004) The genome of Cryptosporidium hominis. Nature 431:1107–1112

    PubMed  CAS  Google Scholar 

  • Yagi T, Seo BB, Di Bernardo S, Nakamaru-Ogiso E, Kao MC, Matsuno-Yagi A (2001) NADH dehydrogenases: from basic science to biomedicine. J Bioenerg Biomembr 33:233–242

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA, 19129, USA

    A. B. Vaidya & M.W. Mather

Authors
  1. A. B. Vaidya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M.W. Mather
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Bloomberg School of Public Health, Department of Molecular Microbiology and Immunology, The Johns Hopkins University, 615 North Wolfe Street, E5628, Baltimore, MD, 21205, USA

    David J. Sullivan M.D.

  2. Department of Cellular and Molecular Medicine, Infectious Diseases Group, St. George’s Hospital Medical School, Cranmer Terrace, London, SW17 ORE, UK

    Sanjeev Krishna D. Phil, F.R.C.P., F. MED. Sci.

  3. Atlanta, Georgia

    R. W. Compans

  4. Birmingham, Alabama

    M. D. Cooper

  5. Kyoto

    T. Honjo

  6. Philadelphia, Pennsylvania

    H. Koprowski

  7. Basel

    F. Melchers

  8. La Jolla, California

    M. B. A. Oldstone

  9. Oslo

    S. Olsnes

  10. Bethesda, Maryland

    M. Potter

  11. La Jolla, California

    P. K. Vogt

  12. Munich

    H. Wagner

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer

About this chapter

Cite this chapter

Vaidya, A.B., Mather, M. (2005). A Post-genomic View of the Mitochondrion in Malaria Parasites. In: Compans, R.W., et al. Malaria: Drugs, Disease and Post-genomic Biology. Current Topics in Microbiology and Immunology, vol 295. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29088-5_9

Download citation

Publish with us

Policies and ethics

Search

Navigation