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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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 http://www.tigr.org. 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.
The authors declare that they have no competing financial interests.
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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) doi:10.1038/nature03149
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