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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/140541
Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide- processing functions of ferredoxin-2 and frataxin
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Iron-sulfur (Fe-S) clusters are essential protein cofactors whose biosynthetic defects lead to severe diseases among which is Friedreich's ataxia caused by impaired expression of frataxin (FXN). Fe-S clusters are biosynthesized on the scaffold protein ISCU, with cysteine desulfurase NFS1 providing sulfur as persulfide and ferredoxin FDX2 supplying electrons, in a process stimulated by FXN but not clearly understood. Here, we report the breakdown of this process, made possible by removing a zinc ion in ISCU that hinders iron insertion and promotes non-physiological Fe-S cluster synthesis from free sulfide in vitro. By binding zinc-free ISCU, iron drives persulfide uptake from NFS1 and allows persulfide reduction into sulfide by FDX2, thereby coordinating sulfide production with its availability to generate Fe-S clusters. FXN stimulates the whole process by accelerating persulfide transfer. We propose that this reconstitution recapitulates physiological conditions which provides a model for Fe-S cluster biosynthesis, clarifies the roles of FDX2 and FXN and may help develop Friedreich's ataxia therapies.
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GERVASON, Sylvain, LARKEM, Djabir, MANSOUR, Amir ben, BOTZANOWSKI, Thomas, MÜLLER, Christina s., PECQUEUR, Ludovic, LE PAVEC, Gwenaelle, DELAUNAY-MOISAN, Agnès, BRUN CUBERO, Omar, AGRAMUNT, Jordi, GRANDAS SAGARRA, Anna, FONTECAVE, Marc, SCHÜNEMANN, Volker, CIANFÉRANI, Sarah, SIZUN, Christina, TOLEDANO, Michel b., D'AUTRÉAUX, Benoit. Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide- processing functions of ferredoxin-2 and frataxin. _Nature Communications_. 2019. Vol. 10, núm. 3566. [consulta: 24 de gener de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/140541]