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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, et al. Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide- processing functions of ferredoxin-2 and frataxin. Nature Communications. 2019. Vol. 10, num. 3566. ISSN 2041-1723. [consulted: 28 of May of 2026]. Available at: https://hdl.handle.net/2445/140541