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Trichomonas hydrogenosomes contain the NADH dehydrogenase module of mitochondrial complex I


Hydrogenosomes are double-membraned ATP-producing and hydrogen-producing organelles of diverse anaerobic eukaryotes1. In some versions of endosymbiotic theory they are suggested to be homologues of mitochondria2,3,4, but alternative views suggest they arose from an anaerobic bacterium that was distinct from the mitochondrial endosymbiont5,6. Here we show that the 51-kDa and 24-kDa subunits of the NADH dehydrogenase module in complex I, the first step in the mitochondrial respiratory chain7, are active in hydrogenosomes of Trichomonas vaginalis. Like mitochondrial NADH dehydrogenase, the purified Trichomonas enzyme can reduce a variety of electron carriers including ubiquinone, but unlike the mitochondrial enzyme it can also reduce ferredoxin, the electron carrier used1 for hydrogen production. The presence of NADH dehydrogenase solves the long-standing conundrum of how hydrogenosomes regenerate NAD+ after malate oxidation. Phylogenetic analyses show that the Trichomonas 51-kDa homologue shares common ancestry with the mitochondrial enzyme. Recruitment of complex I subunits into a H2-producing pathway provides evidence that mitochondria and hydrogenosomes are aerobic and anaerobic homologues of the same endosymbiotically derived organelle.

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Figure 3: Sequences of NuoF and NuoE.
Figure 1: Localization of Trichomonas NADH dehydrogenase subunits.
Figure 2: Localization of Tvh-47 within Trichomonas hydrogenosomes.
Figure 4: Phylogenetic analyses of NuoF homologues.
Figure 5: A schematic diagram illustrating the possible roles of NADH dehydrogenase from complex I in hydrogenosomal metabolism of Trichomonas vaginalis.


  1. 1

    Müller, M. The hydrogenosome. J. Gen. Microbiol. 139, 2879–2889 (1993)

    Article  Google Scholar 

  2. 2

    Embley, T. M., Horner, D. S. & Hirt, R. P. Anaerobic eukaryote evolution: hydrogenosomes as biochemically modified mitochondria? Trends Ecol. Evol. 12, 437–441 (1997)

    CAS  Article  Google Scholar 

  3. 3

    Martin, W. & Müller, M. The hydrogen hypothesis for the first eukaryote. Nature 392, 37–41 (1998)

    ADS  CAS  Article  Google Scholar 

  4. 4

    Embley, T. M. et al. Hydrogenosomes, mitochondria and early eukaryotic evolution. IUBMB Life 55, 387–395 (2003)

    CAS  Article  Google Scholar 

  5. 5

    Whatley, J. M., John, P. & Whatley, F. R. From extracellular to intracellular: the establishment of mitochondria and chloroplasts. Proc. R. Soc. Lond. B 204, 165–187 (1979)

    ADS  CAS  Article  Google Scholar 

  6. 6

    Dyall, S. D., Brown, M. T. & Johnson, P. J. Ancient invasions: from endosymbionts to organelles. Science 304, 253–257 (2004)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Yano, T. The energy-transducing NADH: quinone oxidoreductase, complex I. Mol. Aspects Med. 23, 345–368 (2002)

    CAS  Article  Google Scholar 

  8. 8

    Clemens, D. L. & Johnson, P. J. Failure to detect DNA in hydrogenosomes of Trichomonas vaginalis by nick translation and immunomicroscopy. Mol. Biol. Parasitol. 106, 307–313 (2000)

    CAS  Article  Google Scholar 

  9. 9

    Benchimol, M., Johnson, P. J. & deSouza, W. Morphogenesis of the hydrogenosome: An ultrastructural study. Biol. Cell 87, 197–205 (1996)

    CAS  Article  Google Scholar 

  10. 10

    Sutak, R. et al. Mitochondrial-type assembly of FeS centers in the hydrogenosomes of the amitochondriate eukaryote Trichomonas vaginalis. Proc. Natl Acad. Sci. USA 101, 10368–10373 (2004)

    ADS  CAS  Article  Google Scholar 

  11. 11

    Biagini, G. A., Finlay, B. J. & Lloyd, D. Evolution of the hydrogenosome. FEMS Microbiol. Lett. 155, 133–140 (1997)

    CAS  Article  Google Scholar 

  12. 12

    Dyall, S. D. et al. Presence of a member of the mitochondrial carrier family in hydrogenosomes: conservation of membrane-targeting pathways between hydrogenosomes and mitochondria. Mol. Cell. Biol. 20, 2488–2497 (2000)

    CAS  Article  Google Scholar 

  13. 13

    Plumper, E., Bradley, P. J. & Johnson, P. J. Implications of protein import on the origin of hydrogenosomes. Protist 149, 303–311 (1998)

    CAS  Article  Google Scholar 

  14. 14

    Drmota, T. et al. Iron-ascorbate cleavable malic enzyme from hydrogenosomes of Trichomonas vaginalis: purification and characterization. Mol. Biochem. Parasitol. 83, 221–234 (1996)

    CAS  Article  Google Scholar 

  15. 15

    Whelan, S. & Goldman, N. A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. Mol. Biol. Evol. 18, 691–699 (2001)

    CAS  Article  Google Scholar 

  16. 16

    Shimodaira, H. An approximately unbiased test of phylogenetic tree selection. Syst. Biol. 51, 492–508 (2002)

    Article  Google Scholar 

  17. 17

    Hendy, M. D. & Penny, D. A framework for the quantitative study of evolutionary trees. Syst. Zool. 38, 297–309 (1989)

    Article  Google Scholar 

  18. 18

    Foster, P. G. Modeling compositional heterogeneity. Syst. Biol. 53, 485–495 (2004)

    Article  Google Scholar 

  19. 19

    Dayhoff, M. O., Schwartz, R. M. & Orcutt, B. C. in Atlas of Protein Sequences and Structure (ed. Dayhoff, M. O.) 345–352 (National Biomedical Research Foundation, Washington DC, 1978)

    Google Scholar 

  20. 20

    Martin, W. et al. Gene transfer to the nucleus and the evolution of chloroplasts. Nature 393, 162–165 (1998)

    ADS  CAS  Article  Google Scholar 

  21. 21

    Delsuc, F., Phillips, M. J. & Penny, D. Comment on ‘Hexapod origins: monophyletic or paraphyletic?’. Science 301, 1482–1483 (2003)

    CAS  Article  Google Scholar 

  22. 22

    Steinbuchel, A. & Muller, M. Anaerobic pyruvate metabolism of Tritrichomonas foetus and Trichomonas vaginalis hydrogenosomes. Mol. Biochem. Parasitol. 20, 57–65 (1986)

    CAS  Article  Google Scholar 

  23. 23

    Rasoloson, D. et al. Mechanisms of in vitro development of resistance to metronidazole in Trichomonas vaginalis. Microbiology 148, 2467–2477 (2002)

    CAS  Article  Google Scholar 

  24. 24

    Pilkington, S. J., Skehel, J. M., Gennis, R. B. & Walker, J. E. Relationship between mitochondrial NADH-ubiquinone reductase and a bacterial NAD-reducing hydrogenase. Biochemistry 30, 2166–2175 (1991)

    CAS  Article  Google Scholar 

  25. 25

    Owen, R. Lectures on the Comparative Physiology of the Invertebrate Animals (Longman, Brown, Green, Longmans, London, 1843)

    Google Scholar 

  26. 26

    Embley, T. M. et al. Multiple origins of anaerobic ciliates with hydrogenosomes within the radiation of aerobic ciliates. Proc. R. Soc. Lond. B 262, 87–93 (1995)

    ADS  CAS  Article  Google Scholar 

  27. 27

    Rotte, C., Stejskal, F., Zhu, G., Keithly, J. S. & Martin, W. Pyruvate: NADP oxidoreductase from the mitochondrion of Euglena gracilis and from the apicomplexan Cryptosporidium parvum: A biochemical relic linking pyruvate metabolism in mitochondriate and amitochondriate protists. Mol. Biol. Evol. 18, 710–720 (2001)

    CAS  Article  Google Scholar 

  28. 28

    Tachezy, J., Sanchez, L. B. & Muller, 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)

    CAS  Article  Google Scholar 

  29. 29

    Ronquist, F. & Huelsenbeck, J. P. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19, 1572–1574 (2003)

    CAS  Article  Google Scholar 

  30. 30

    Gaziova, I. & Lukes, J. Mitochondrial and nuclear localization of topoisomerase II in the flagellate Bodo saltans (Kinetoplastida), a species with non-catenated kinetoplast DNA. J. Biol. Chem. 278, 10900–10907 (2003)

    CAS  Article  Google Scholar 

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We thank M. Hubalek for mass spectrometry and P. Dyal for technical support. Sequence data for Trichomonas vaginalis were obtained from The Institute for Genomic Research website at Sequencing of T. vaginalis was accomplished with support from The National Institute of Allergy and Infectious Diseases. This work was supported by a Fogarty International Research Collaboration Award to J.T. and Miklos Muller and a grant from the Grant Agency of the Czech Republic to J.T. R.P.H. was supported by a Wellcome Trust University Award.

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Corresponding authors

Correspondence to Jan Tachezy or T. Martin Embley.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure 1

Diagram of the 5 supplementary phylogenetic trees listed in the Table S1 found in the below Supplementary Materials. (PDF 265 kb)

Supplementary Material

Supplementary Tables (S1–S4), and Supplementary Methods for enzyme assays and purification. (DOC 41 kb)

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Hrdy, I., Hirt, R., Dolezal, P. et al. Trichomonas hydrogenosomes contain the NADH dehydrogenase module of mitochondrial complex I. Nature 432, 618–622 (2004).

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