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Mitochondrial remnant organelles of Giardia function in iron-sulphur protein maturation

Nature volume 426, pages 172176 (13 November 2003) | Download Citation



Giardia intestinalis (syn. lamblia) is one of the most widespread intestinal protozoan pathogens worldwide, causing hundreds of thousands of cases of diarrhoea each year1. Giardia is a member of the diplomonads, often described as an ancient protist group whose primitive nature is suggested by the lack of typical eukaryotic organelles (for example, mitochondria, peroxisomes), the presence of a poorly developed endomembrane system and by their early branching in a number of gene phylogenies1,2. The discovery of nuclear genes of putative mitochondrial ancestry in Giardia3,4,5,6,7 and the recent identification of mitochondrial remnant organelles in amitochondrial protists such as Entamoeba histolytica8,9 and Trachipleistophora hominis10 suggest that the eukaryotic amitochondrial state is not a primitive condition but is rather the result of reductive evolution. Using an in vitro protein reconstitution assay and specific antibodies against IscS and IscU—two mitochondrial marker proteins involved in iron–sulphur cluster biosynthesis—here we demonstrate that Giardia contains mitochondrial remnant organelles (mitosomes) bounded by double membranes that function in iron–sulphur protein maturation. Our results indicate that Giardia is not primitively amitochondrial and that it has retained a functional organelle derived from the original mitochondrial endosymbiont.

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  1. 1.

    Biology of Giardia lamblia. Clin. Microbiol. Rev. 14, 447–475 (2001)

  2. 2.

    & Evolution of the protists and protistan parasites from the perspective of molecular systematics. Int. J. Parasitol. 28, 11–20 (1998)

  3. 3.

    , , , & Secondary absence of mitochondria in Giardia lamblia and Trichomonas vaginalis revealed by valyl-tRNA synthetase phylogeny. Proc. Natl Acad. Sci. USA 95, 6860–6865 (1998)

  4. 4.

    et al. A mitochondrial-like chaperonin 60 gene in Giardia lamblia: evidence that diplomonads once harbored an endosymbiont related to the progenitor of mitochondria. Proc. Natl Acad. Sci. USA 95, 229–234 (1998)

  5. 5.

    , & Mitochondrial type iron-sulfur cluster assembly in the amitochondriate eukaryotes Trichomonas vaginalis and Giardia intestinalis, as indicated by the phylogeny of IscS. Mol. Biol. Evol. 18, 1919–1928 (2001)

  6. 6.

    , , , & Giardia lamblia expresses a proteobacterial-like DnaK homolog. Mol. Biol. Evol. 18, 530–541 (2001)

  7. 7.

    , , , & Mitochondrial-type hsp70 genes of the amitochondriate protists Giardia intestinalis, Entamoeba histolytica and two microsporidians. Parasitol. Int. 51, 9–16 (2002)

  8. 8.

    et al. Hsp60 is targeted to a cryptic mitochondrion-derived organelle (“crypton”) in the microaerophilic protozoan parasite Entamoeba histolytica. Mol. Cell. Biol. 19, 2198–2205 (1999)

  9. 9.

    , & The mitosome, a novel organelle related to mitochondria in the amitochondrial parasite Entamoeba histolytica. Mol. Microbiol. 32, 1013–1021 (1999)

  10. 10.

    , , & A mitochondrial remnant in the microsporidian Trachipleistophora hominis. Nature 418, 865–869 (2002)

  11. 11.

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

  12. 12.

    in Molecular Medical Parasitology (eds Marr, J., Nilsen, T. & Komuniecki, R.) 125–139 (Academic, London, 2003)

  13. 13.

    & Origins of hydrogenosomes and mitochondria: evolution and organelle biogenesis. Curr. Opin. Microbiol. 3, 404–411 (2000)

  14. 14.

    , , , & Mitochondria and hydrogenosomes are two forms of the same fundamental organelle. Phil. Trans. R. Soc. Lond. 358, 191–203 (2003)

  15. 15.

    & Giardia: highly evolved parasite or early branching eukaryote? Trends Microbiol. 10, 122–127 (2002)

  16. 16.

    & Presence and cellular distribution of a 60-kDa protein related to mitochondrial hsp60 in Giardia lamblia. J. Parasitol. 80, 580–590 (1994)

  17. 17.

    et al. Network of protein-protein interactions among iron-sulfur cluster assembly proteins in Escherichia coli. J. Biochem. (Tokyo) 131, 713–719 (2002)

  18. 18.

    & Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells. EMBO J. 19, 5692–5700 (2000)

  19. 19.

    , , , & Phylogenetic analyses of diplomonad genes reveal frequent lateral gene transfers affecting eukaryotes. Curr. Biol. 13, 94–104 (2003)

  20. 20.

    You are what you eat: a gene transfer ratchet could account for bacterial genes in eukaryotic nuclear genomes. Trends Genet. 14, 307–311 (1998)

  21. 21.

    et al. The ‘primitive’ microaerophile Giardia intestinalis (syn. lamblia, duodenalis) has specialized membranes with electron transport and membrane-potential-generating functions. Microbiology 148, 1349–1354 (2002)

  22. 22.

    , , & Cryptosporidium parvum Cpn60 targets a relict organelle. Curr. Genet. advance online publication, 20 August 2003 (doi:10.1007/s00294-003-0432-1)

  23. 23.

    et al. Early-branching or fast-evolving eukaryotes? An answer based on slowly evolving positions. Proc. R. Soc. Lond. B 267, 1213–1221 (2000)

  24. 24.

    , , & An overview of endosymbiotic models for the origins of eukaryotes, their ATP-producing organelles (mitochondria and hydrogenosomes), and their heterotrophic lifestyle. Biol. Chem. 382, 1521–1539 (2001)

  25. 25.

    et al. Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414, 450–453 (2001)

  26. 26.

    et al. The Giardia genome project database. FEMS Microbiol. Lett. 189, 271–273 (2000)

  27. 27.

    & Preliminary profile of the Cryptosporidium parvum genome: an expressed sequence tag and genome survey sequence analysis. Mol. Biochem. Parasitol. 107, 1–32 (2000)

  28. 28.

    , & Giardia intestinalis, a eukaryote without hydrogenosomes, produces hydrogen. Microbiology 148, 727–733 (2002)

  29. 29.

    , & Expression and spectroscopic characterization of the hydrogenosomal [2Fe-2S] ferredoxin from the protozoan Trichomonas vaginalis. J. Biol. Chem. 271, 14734–14739 (1996)

  30. 30.

    , , , & Distinct compartmentalization of TGN46 and beta 1,4-galactosyl transferase in HeLa cells. Eur. J. Cell Biol. 72, 238–246 (1997)

  31. 31.

    Sampling Techniques (John Wiley and Sons, London, 1977)

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We thank G. Clark, J. Bowyer and S. Cutting for critically reading the manuscript. A recombinant plasmid containing the T. vaginalis ferredoxin gene was provided by J. P. Germanas and K. Krause. The use of partial genome sequence information from the Giardia Genome Project Database26 is acknowledged. The technical assistance of J. James and N. Sommerville is also acknowledged. M.H. is a sabbatical visitor supported by CINVESTAV, México. Research at the Rockefeller University (gene cloning, antibody generation) was supported by a NIH grant to M.M. Research at Charles University (in vitro assembly of Fe–S clusters) was supported by a grant from FIRCA to J.Tachezy. J.M.L. (electron microscopy) was supported by a Research Leave Fellowship from the Wellcome Trust and by Tenovus Scotland. Research at Royal Holloway (bioinformatics, cell fractionation, fluorescence confocal microscopy, manuscript writing, project coordination) was supported by a Wellcome Trust grant to J.Tovar.

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Author notes

    • Lidya B Sánchez

    Present address: Public Health Research Institute, Newark, New Jersey 07103, USA


  1. School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK

    • Jorge Tovar
    • , Gloria León-Avila
    • , Mark van der Giezen
    •  & Manuel Hernández
  2. The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA

    • Lidya B Sánchez
    •  & Miklós Müller
  3. Department of Parasitology, Faculty of Science, Charles University, 12844 Prague 2, Czech Republic

    • Robert Sutak
    •  & Jan Tachezy
  4. School of Life Sciences, WTB/MSI complex, University of Dundee, Dundee DD1 5EH, UK

    • John M. Lucocq


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The authors declare that they have no competing financial interests.

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Correspondence to Jorge Tovar.

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