Skip to Main content Skip to Navigation
Journal articles

Mammalian frataxin directly enhances sulfur transfer of NFS1 persulfide to both ISCU and free thiols.

Abstract : Friedreich's ataxia is a severe neurodegenerative disease caused by the decreased expression of frataxin, a mitochondrial protein that stimulates iron-sulfur (Fe-S) cluster biogenesis. In mammals, the primary steps of Fe-S cluster assembly are performed by the NFS1-ISD11-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 compounds 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-ISD11-ISCU complex.
Document type :
Journal articles
Complete list of metadatas

https://hal.archives-ouvertes.fr/hal-01111365
Contributor : Jocelyne Brunet <>
Submitted on : Friday, January 30, 2015 - 11:26:02 AM
Last modification on : Monday, June 22, 2020 - 12:08:08 PM

Identifiers

  • HAL Id : hal-01111365, version 1
  • PUBMED : 25597503

Collections

Citation

Aubérie Parent, Xavier Elduque, David Cornu, Laura Belot, Jean-Pierre Le Caer, et al.. Mammalian frataxin directly enhances sulfur transfer of NFS1 persulfide to both ISCU and free thiols.. Nature Communications, Nature Publishing Group, 2014, 6, pp.5686. ⟨hal-01111365⟩

Share

Metrics

Record views

162