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bioRxiv · 10.1101/2024.05.01.592079

HCF101 is a novel component of the CIA cytosolic iron-sulfur synthesis pathway in the human pathogen Toxoplasma gondii

Renaud, E. A.·Maupin, A. J.·Berry, L.·Bals, J.·Bordat, Y.·Demolombe, V.·Rofidal, V.·Vignols, F.·Besteiro, S.
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Abstract

Several key cellular functions depend on proteins harboring an iron-sulfur (Fe-S) cofactor. As these Fe-S proteins localize to several subcellular compartments, they require a dedicated machinery for cofactor assembly. For instance, in plants and algae there are Fe-S cluster synthesis pathways localizing to the cytosol, but also present in the mitochondrion and in the chloroplast, two organelles of endosymbiotic origin. Toxoplasma gondii is a plastid-bearing parasitic protist responsible for a pathology affecting humans and other warm-blooded vertebrates. We have characterized the Toxoplasma homologue of HCF101, originally identified in plants as a protein transferring Fe-S clusters to photosystem I subunits in the chloroplast. Contrarily to plants, we have shown that HCF101 does not localize to the plastid in parasites, but instead is an important component of the cytosolic Fe-S assembly (CIA) pathway which is vital for Toxoplasma. While the CIA pathway is widely conserved in eukaryotes, it is the first time the involvement of HCF101 in this pan-eukaryotic machinery is established. Moreover, as this protein is essential for parasite viability and absent from its mammalian hosts, it constitutes a novel and promising potential drug target.

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Renaud, E. A., Maupin, A. J., Berry, L., Bals, J., Bordat, Y., Demolombe, V., Rofidal, V., Vignols, F., Besteiro, S.. 2024-05-01. HCF101 is a novel component of the CIA cytosolic iron-sulfur synthesis pathway in the human pathogen Toxoplasma gondii. https://doi.org/10.1101/2024.05.01.592079

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