# name
Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide- processing functions of ferredoxin-2 and frataxin

# metadata.dc.description.abstract[].value
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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Nature Communications, 2019, vol. 10, p. 3566

# metadata.dc.rights[].value
cc-by (c) Gervason, Sylvain et al., 2019

# metadata.dc.source[].value
Articles publicats en revistes (Química Inorgànica i Orgànica)

# metadata.dc.title[].value
Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide- processing functions of ferredoxin-2 and frataxin