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

Abstract

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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Figure 1: Distribution of IscU and IscS in Giardia cell extracts.
Figure 2: Functional analysis of Fe–S protein maturation in Giardia.
Figure 3: Localization of IscS and IscU in Giardia trophozoites by confocal immunofluorescence microscopy.
Figure 4: Localization of IscS and IscU in Giardia trophozoites by transmission electron immunomicroscopy.

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References

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Hashimoto, T., Sánchez, L. B., Shirakura, T., Müller, M. & Hasegawa, M. 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)

    Article  ADS  CAS  Google Scholar 

  4. Roger, A. J. 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)

    Article  ADS  CAS  Google Scholar 

  5. Tachezy, J., Sánchez, L. B. & Müller, M. 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)

    Article  CAS  Google Scholar 

  6. Morrison, H. G., Roger, A. J., Nystul, T. G., Gillin, F. D. & Sogin, M. L. Giardia lamblia expresses a proteobacterial-like DnaK homolog. Mol. Biol. Evol. 18, 530–541 (2001)

    Article  CAS  Google Scholar 

  7. Arisue, N., Sánchez, L. B., Weiss, L. M., Müller, M. & Hashimoto, T. Mitochondrial-type hsp70 genes of the amitochondriate protists Giardia intestinalis, Entamoeba histolytica and two microsporidians. Parasitol. Int. 51, 9–16 (2002)

    Article  CAS  Google Scholar 

  8. Mai, Z. 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)

    Article  CAS  Google Scholar 

  9. Tovar, J., Fischer, A. & Clark, C. G. The mitosome, a novel organelle related to mitochondria in the amitochondrial parasite Entamoeba histolytica. Mol. Microbiol. 32, 1013–1021 (1999)

    Article  CAS  Google Scholar 

  10. Williams, B. A. P., Hirt, R. P., Lucocq, J. M. & Embley, T. M. A mitochondrial remnant in the microsporidian Trachipleistophora hominis. Nature 418, 865–869 (2002)

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Book  Google Scholar 

  13. Dyall, S. D. & Johnson, P. J. Origins of hydrogenosomes and mitochondria: evolution and organelle biogenesis. Curr. Opin. Microbiol. 3, 404–411 (2000)

    Article  CAS  Google Scholar 

  14. Embley, T. M., van der Giezen, M., Horner, D. S., Dyal, P. L. & Foster, P. Mitochondria and hydrogenosomes are two forms of the same fundamental organelle. Phil. Trans. R. Soc. Lond. 358, 191–203 (2003)

    Article  CAS  Google Scholar 

  15. Lloyd, D. & Harris, J. C. Giardia: highly evolved parasite or early branching eukaryote? Trends Microbiol. 10, 122–127 (2002)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Andersson, J. O., Sjogren, A. M., Davis, L. A., Embley, T. M. & Roger, A. J. Phylogenetic analyses of diplomonad genes reveal frequent lateral gene transfers affecting eukaryotes. Curr. Biol. 13, 94–104 (2003)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  21. Lloyd, D. 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)

    Article  CAS  Google Scholar 

  22. Riordan, C. E., Ault, J. G., Langreth, S. G. & Keithly, J. S. Cryptosporidium parvum Cpn60 targets a relict organelle. Curr. Genet. advance online publication, 20 August 2003 (doi:10.1007/s00294-003-0432-1)

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

    Article  CAS  Google Scholar 

  24. Martin, W., Hoffmeister, M., Rotte, C. & Henze, K. 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)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  28. Lloyd, D., Ralphs, J. R. & Harris, J. C. Giardia intestinalis, a eukaryote without hydrogenosomes, produces hydrogen. Microbiology 148, 727–733 (2002)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  30. Prescott, A. R., Lucocq, J. M., James, J., Lister, J. M. & Ponnambalam, S. Distinct compartmentalization of TGN46 and beta 1,4-galactosyl transferase in HeLa cells. Eur. J. Cell Biol. 72, 238–246 (1997)

    CAS  PubMed  Google Scholar 

  31. Cochran, W. G. Sampling Techniques (John Wiley and Sons, London, 1977)

    MATH  Google Scholar 

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Acknowledgements

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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Correspondence to Jorge Tovar.

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Tovar, J., León-Avila, G., Sánchez, L. et al. Mitochondrial remnant organelles of Giardia function in iron-sulphur protein maturation. Nature 426, 172–176 (2003). https://doi.org/10.1038/nature01945

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