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Title: Mammalian frataxin directly enhances sulfur transfer of NFS1 persulfide to both ISCU and free thiols
Author: Parent, Aubérie
Elduque Busquets, Xavier
Cornu, David
Belot, Laura
Le Caer, Jean-Pierre
Grandas Sagarra, Anna
Toledano, Michel B.
D'Autréaux, Benoit
Keywords: Bioquímica
Malalties neurodegeneratives
Neurodegenerative diseases
Issue Date: 19-Jan-2014
Publisher: Nature Publishing Group
Abstract: Friedreich'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.
Note: Versió postprint del document publicat a:
It is part of: Nature Communications, 2014, vol. 6
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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