2026-04-17T03:29:32Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1405412025-12-04T21:44:49Zcom_2072_1057col_2072_478917col_2072_478933

00925njm 22002777a 4500 dc Gervason, Sylvain author Larkem, Djabir author Mansour, Amir Ben author Botzanowski, Thomas author Müller, Christina S. author Pecqueur, Ludovic author Le Pavec, Gwenaelle author Delaunay-Moisan, Agnès author Brun Cubero, Omar author Agramunt, Jordi author Grandas Sagarra, Anna author Fontecave, Marc author Schünemann, Volker author Cianférani, Sarah author Sizun, Christina author Toledano, Michel B. author D'Autréaux, Benoit author 2019-09-19T14:47:35Z 2019-09-19T14:47:35Z 2019 2019-09-19T14:47:36Z 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. Malalties neurodegeneratives Bioquímica Biosíntesi Proteïnes Neurodegenerative Diseases Biochemistry Biosynthesis Proteins Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide- processing functions of ferredoxin-2 and frataxin