Parent, AubérieElduque Busquets, XavierCornu, DavidBelot, LauraLe Caer, Jean-PierreGrandas Sagarra, AnnaToledano, Michel B.D'Autréaux, Benoit2015-10-082015-10-082014-01-192041-1723https://hdl.handle.net/2445/67192Friedreich's ataxia is a severe neurodegenerative disease caused by the decreased expression of frataxin, a mitochondrial protein that stimulates iron <br>sulfur (Fe-S) cluster biogenesis. In mammals, the primary steps of Fe-S cluster assembly are performed by the NFS1 <br>ISD11 <br>ISCU complex via the formation of a persulfide intermediate on NFS1. Here we show that frataxin modulates the reactivity of NFS1 persulfide with thiols. We use maleimide-peptide com- pounds along with mass spectrometry to probe cysteine-persulfide in NFS1 and ISCU. Our data reveal that in the presence of ISCU, frataxin enhances the rate of two similar reactions on NFS1 persulfide: sulfur transfer to ISCU leading to the accumulation of a persulfide on the cysteine C104 of ISCU, and sulfur transfer to small thiols such as DTT, L-cysteine and GSH leading to persulfuration of these thiols and ultimately sulfide release. These data raise important questions on the physiological mechanism of Fe-S cluster assembly and point to a unique function of frataxin as an enhancer of sulfur transfer within the NFS1 <br>ISD11 <br>ISCU complex.12 p.application/pdfeng(c) Parent et al., 2014BioquímicaMalalties neurodegenerativesProteïnesBiochemistryNeurodegenerative DiseasesProteinsinfo:eu-repo/semantics/article6520802015-10-08info:eu-repo/semantics/openAccess25597503