Turning into a Frataxin-Dependent Organism

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Iron sulfur (Fe-S) clusters are ubiquitous cofactors found in proteins which function in very diverse pathways ranging from respiration to DNA repair. The mitochondrial Fe-S biogenesis machinery ISC was inherited from the bacterial ancestor of mitochondria. In both prokaryotes and eukaryotes, deficiency of core ISC components is associated with drastic decrease in Fe-S proteins activities and causes severe phenotypes. In this context, the case of frataxin, an ISC associated component, is surprising since the lack of frataxin in prokaryotes leads to very mild phenotypes in comparison to eukaryotes. Here, we showed that in an E. coli strain, a single mutation in a key component of the Fe-S cluster biogenesis pathway, namely the scaffold protein, was sufficient to impose a strict frataxin dependency. Remarkably, this mutation substituted an Ile residue that is conserved in prokaryotic scaffolds, for one Met residue that is conserved in eukaryotic scaffolds. These results provide a lead towards understanding the differences between otherwise highly related prokaryotic and eukaryotic ISC Fe-S cluster biogenesis machineries, and provide a new entry point into deciphering the molecular role of frataxin.

Vyšlo v časopise: Turning into a Frataxin-Dependent Organism. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005134
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005134

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