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


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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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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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).

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