Recent data suggest that frataxin plays a key role in eukaryote cellular iron metabolism, particularly in mitochondrial heme and iron-sulfur (FeS) cluster biosynthesis. We have now identified a frataxin homologue (T. vaginalis frataxin) from the human parasite Trichomonas vaginalis. Instead of mitochondria, this unicellular eukaryote possesses hydrogenosomes, peculiar organelles that produce hydrogen but nevertheless share common ancestry with mitochondria. T. vaginalis frataxin contains conserved residues implicated in iron binding, and in silico, it is predicted to form a typical alpha-beta sandwich motif. The short N-terminal extension of T. vaginalis frataxin resembles presequences that target proteins to hydrogenosomes, a prediction confirmed by the results of overexpression of T. vaginalis frataxin in T. vaginalis. When expressed in the mitochondria of a frataxin-deficient Saccharomyces cerevisiae strain, T. vaginalis frataxin partially restored defects in heme and FeS cluster biosynthesis. Although components of heme synthesis or heme-containing proteins have not been found in T. vaginalis to date, T. vaginalis frataxin was also shown to interact with S. cerevisiae ferrochelatase by using a Biacore assay. The discovery of conserved iron-metabolizing pathways in mitochondria and hydrogenosomes provides additional evidence not only of their common evolutionary history, but also of the fundamental importance of this pathway for eukaryotes.

Department of Parasitology Charles University Faculty of Science Vinicna 7 128 44 Prague Czech Republic

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Adaptation of the late ISC pathway in the anaerobic mitochondrial organelles of Giardia intestinalis

Inheritance of the reduced mitochondria of Giardia intestinalis is coupled to the flagellar maturation cycle

Fe-S cluster assembly in the supergroup Excavata

Transcriptomic identification of iron-regulated and iron-independent gene copies within the heavily duplicated Trichomonas vaginalis genome

Live imaging of mitosomes and hydrogenosomes by HaloTag technology

The monothiol single-domain glutaredoxin is conserved in the highly reduced mitochondria of Giardia intestinalis

Mitochondrial localization of human frataxin is necessary but processing is not for rescuing frataxin deficiency in Trypanosoma brucei