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Non-mitochondrial complex I proteins in a hydrogenosomal oxidoreductase complex

Nature volume 431, pages 1103–1107 (2004)Cite this article

Abstract

Trichomonas vaginalis is a unicellular microaerophilic eukaryote that lacks mitochondria yet contains an alternative organelle, the hydrogenosome, involved in pyruvate metabolism. Pathways between the two organelles differ substantially: in hydrogenosomes, pyruvate oxidation is catalysed by pyruvate:ferredoxin oxidoreductase (PFOR), with electrons donated to an [Fe]-hydrogenase which produces hydrogen. ATP is generated exclusively by substrate-level phosphorylation in hydrogenosomes, as opposed to oxidative phosphorylation in mitochondria1. PFOR and hydrogenase are found in eubacteria and amitochondriate eukaryotes, but not in typical mitochondria2,3,4. Analyses of mitochondrial genomes indicate that mitochondria have a single endosymbiotic origin from an α-proteobacterial-type progenitor5. The absence of a genome in trichomonad hydrogenosomes6 precludes such comparisons, leaving the endosymbiotic history of this organelle unclear7. Although phylogenetic reconstructions of a few proteins indicate that trichomonad hydrogenosomes share a common origin with mitochondria8,9,10,11, others do not2,3,4,7. Here we describe a novel NADH dehydrogenase module of respiratory complex I that is coupled to the central hydrogenosomal fermentative pathway to form a hydrogenosomal oxidoreductase complex that seems to function independently of quinones. Phylogenetic analyses of hydrogenosomal complex I-like proteins Ndh51 and Ndh24 reveal that neither has a common origin with mitochondrial homologues. These studies argue against a vertical origin of trichomonad hydrogenosomes from the proto-mitochondrial endosymbiont.

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Figure 1: Complex I proteins.
Figure 2: T. vaginalis Ndh protein–protein interactions.
Figure 3: Hydrogenosomal carbohydrate metabolism.
Figure 4: Analyses of NuoF and NuoE phylogenies with MRBAYES30 show that T. vaginalis Ndh51 and Ndh24 do not belong to the mitochondrial clade.

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References

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

    Article  Google Scholar 

  2. Horner, D. S., Hirt, R. P. & Embley, T. M. A single eubacterial origin of eukaryotic pyruvate: ferredoxin oxidoreductase genes: implications for the evolution of anaerobic eukaryotes. Mol. Biol. Evol. 16, 1280–1291 (1999)

    Article  CAS  Google Scholar 

  3. Horner, D. S., Foster, P. G. & Embley, T. M. Iron hydrogenases and the evolution of anaerobic eukaryotes. Mol. Biol. Evol. 17, 1695–1709 (2000)

    Article  CAS  Google Scholar 

  4. 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. B 358, 191–201 (2003)

    Article  CAS  Google Scholar 

  5. Gray, M. W., Burger, G. & Lang, B. F. Mitochondrial evolution. Science 283, 1476–1481 (1999)

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  8. Bui, E. T. N., Bradley, P. J. & Johnson, P. J. A common evolutionary origin for mitochondria and hydrogenosomes. Proc. Natl Acad. Sci. USA 93, 9651–9656 (1996)

    Article  ADS  CAS  Google Scholar 

  9. Horner, D. S., Hirt, R. P., Kilvington, S., Lloyd, D. & Embley, T. M. Molecular data suggest an early acquisition of the mitochondrion endosymbiont. Proc. R. Soc. Lond. B 263, 1053–1059 (1996)

    Article  ADS  CAS  Google Scholar 

  10. Roger, A. J., Clark, C. G. & Doolittle, W. F. A possible mitochondrial gene in the early-branching amitochondriate protist Trichomonas vaginalis. Proc. Natl Acad. Sci. USA 93, 14618–14622 (1996)

    Article  ADS  CAS  Google Scholar 

  11. 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)

    Article  CAS  Google Scholar 

  12. Friedrich, T. & Bottcher, B. The gross structure of the respiratory complex I: a Lego System. Biochim. Biophys. Acta 1608, 1–9 (2004)

    Article  CAS  Google Scholar 

  13. Fearnley, I. M. & Walker, J. E. Conservation of sequences of subunits of mitochondrial complex I and their relationships with other proteins. Biochim. Biophys. Acta 1140, 105–134 (1992)

    Article  CAS  Google Scholar 

  14. Yano, T., Sled, V. D., Ohnishi, T. & Yagi, T. Identification of amino acid residues associated with the [2Fe–2S] cluster of the 25 kDa (NQO2) subunit of the proton-translocating NADH-quinone oxidoreductase of Paracoccus denitrificans. FEBS Lett. 354, 160–164 (1994)

    Article  CAS  Google Scholar 

  15. Yano, T., Sled, V. D., Ohnishi, T. & Yagi, T. Expression and characterization of the flavoprotein subcomplex composed of 50-kDa (NQO1) and 25-kDa (NQO2) subunits of the proton-translocating NADH-quinone oxidoreductase of Paracoccus denitrificans. J. Biol. Chem. 271, 5907–5913 (1996)

    Article  CAS  Google Scholar 

  16. Hrdy, I. & Müller, M. Primary structure of the hydrogenosomal malic enzyme of Trichomonas vaginalis and its relationship to homologous enzymes. J. Eukaryot. Microbiol. 2, 593–603 (1995)

    Article  Google Scholar 

  17. Hrdy, I. & Müller, M. Primary structure and eubacterial relationships of the pyruvate:ferredoxin oxidoreductase of the amitochondriate eukaryote Trichomonas vaginalis. J. Mol. Evol. 41, 388–396 (1995)

    Article  ADS  CAS  Google Scholar 

  18. Dolezal, P., Vanacova, S., Tachezy, J. & Hrdy, I. Malic enzymes of Trichomonas vaginalis: two enzyme families, two distinct origins. Gene 329, 81–92 (2004)

    Article  CAS  Google Scholar 

  19. Jonassen, T., Davis, D. E., Larsen, P. L. & Clarke, C. F. Reproductive fitness and quinone content of Caenorhabditis elegans clk-1 mutants fed coenzyme Q isoforms of varying length. J. Biol. Chem. 278, 51735–51742 (2003)

    Article  CAS  Google Scholar 

  20. Meganathan, R. Ubiquinone biosynthesis in microorganisms. FEMS Microbiol. Lett. 203, 131–139 (2001)

    Article  CAS  Google Scholar 

  21. Massanz, C., Schmidt, S. & Friedrich, B. Subforms and in vitro reconstitution of the NAD-reducing hydrogenase of Alcaligenes eutrophus. J. Bacteriol. 180, 1023–1029 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Land, K. M. et al. Targeted gene replacement of a ferredoxin gene in Trichomonas vaginalis does not lead to metronidazole resistance. Mol. Microbiol. 51, 115–122 (2004)

    Article  CAS  Google Scholar 

  23. Friedrich, T. & Scheide, D. The respiratory complex I of bacteria, archaea and eukarya and its module common with membrane-bound multisubunit hydrogenases. FEBS Lett. 479, 1–5 (2000)

    Article  CAS  Google Scholar 

  24. Lang, B. F. et al. An ancestral mitochondrial DNA resembling a eubacterial genome in miniature. Nature 387, 493–497 (1997)

    Article  CAS  Google Scholar 

  25. Andersson, S. G. et al. The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396, 133–140 (1998)

    Article  ADS  CAS  Google Scholar 

  26. Akhmanova, A. et al. A hydrogenosome with a genome. Nature 396, 527–528 (1998)

    Article  ADS  CAS  Google Scholar 

  27. Doolittle, W. F. et al. How big is the iceberg of which organellar genes in nuclear genomes are but the tip? Phil. Trans. R. Soc. Lond. B 358, 39–57 (2003)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  29. 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 

  30. Huelsenbeck, J. P. & Ronquist, F. MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 17, 754–755 (2001)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank J. L. Kerwin for mass spectrometric analyses. Preliminary T. vaginalis genome sequence data were obtained from TIGR through the website at http://www.tigr.org. Sequencing of the T. vaginalis genome was accomplished with support from the NIH. This work was supported by National Institute of Health (NIH) grants (P.J.J. and C.F.C.) and a National Aeronautics and Space Administration Astrobiology grant to UCLA. P.J.J. is a Burroughs Wellcome Scholar in Molecular Parasitology. The UCLA Mass Spectrometry and Proteomics Technology Center (J.A.L.) was established with a grant from the W. M. Keck Foundation.

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Authors and Affiliations

  1. Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, 1602 Molecular Sciences Building, 609 Charles E. Young Drive East, Los Angeles, California, 90095-1489, USA

    Sabrina D. Dyall, Weihong Yan, Maria G. Delgadillo-Correa & Patricia J. Johnson

  2. NASA Astrobiology Institute, Center for Astrobiology/IGPP, 3845 Slichter Hall, Los Angeles, California, 90095-1567, USA

    Sabrina D. Dyall & Patricia J. Johnson

  3. Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, California, 90095-1569, USA

    Weihong Yan, Adam Lunceford & Catherine F. Clarke

  4. Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, 402 Paul D. Boyer Hall, Los Angeles, California, 90095-1737, USA

    Joseph A. Loo

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Correspondence to Patricia J. Johnson.

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Supplementary information

Supplementary Figure 1

Alignment of T. vaginalis malic enzyme subunits Mae A, B, G, H using CLUSTALW. (DOC 34 kb)

Supplementary Figure 2

Reconstruction of NuoE phylogeny excluding highly divergent sequences. This phylogenetic reconstruction of NuoE sequences shows that the position of T. vaginalis Ndh24 is not due to a long-branch artefact. (JPG 93 kb)

Supplementary Figure 2 Legend (DOC 31 kb)

Supplementary Table 1

Primer sequences used in study. (DOC 27 kb)

Supplementary Table 2

List of sequences used to reconstruct Ndh51 phylogeny, with names and accession numbers. (DOC 61 kb)

Supplementary Table 3

List of sequences used to reconstruct Ndh24 phylogeny, with names and accession numbers. (DOC 53 kb)

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Dyall, S., Yan, W., Delgadillo-Correa, M. et al. Non-mitochondrial complex I proteins in a hydrogenosomal oxidoreductase complex. Nature 431, 1103–1107 (2004). https://doi.org/10.1038/nature02990

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