Mammalian frataxin controls sulfur production and iron entry during de novo Fe4S4 cluster assembly. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of the American Chemical Society Année : 2013

Mammalian frataxin controls sulfur production and iron entry during de novo Fe4S4 cluster assembly.

Résumé

Iron-sulfur (Fe-S) cluster-containing proteins are essential components of cells. In eukaryotes, Fe-S clusters are synthesized by the mitochondrial iron-sulfur cluster (ISC) machinery and the cytosolic iron-sulfur assembly (CIA) system. In the mammalian ISC machinery, preassembly of the Fe-S cluster on the scaffold protein (ISCU) involves a cysteine desulfurase complex (NFS1/ISD11) and frataxin (FXN), the protein deficient in Friedreich's ataxia. Here, by comparing the biochemical and spectroscopic properties of quaternary (ISCU/NFS1/ISD11/FXN) and ternary (ISCU/NFS1/ISD11) complexes, we show that FXN stabilizes the quaternary complex and controls iron entry to the complex through activation of cysteine desulfurization. Furthermore, we show for the first time that in the presence of iron and L-cysteine, an [Fe(4)S(4)] cluster is formed within the quaternary complex that can be transferred to mammalian aconitase (mACO2) to generate an active enzyme. In the absence of FXN, although the ternary complex can assemble an Fe-S cluster, the cluster is inefficiently transferred to ACO2. Taken together, these data help to unravel further the Fe-S cluster assembly process and the molecular basis of Friedreich's ataxia.
Fichier non déposé

Dates et versions

hal-01054359 , version 1 (06-08-2014)

Identifiants

Citer

Florent Colin, Alain Martelli, Martin Clémancey, Jean-Marc Latour, Serge Gambarelli, et al.. Mammalian frataxin controls sulfur production and iron entry during de novo Fe4S4 cluster assembly.. Journal of the American Chemical Society, 2013, 135 (2), pp.733-40. ⟨10.1021/ja308736e⟩. ⟨hal-01054359⟩
137 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More