title: Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron-sulfur assembly complex.
abstract: BACKGROUND
  Frataxin, the mitochondrial protein deficient in Friedreich ataxia, a rare autosomal recessive neurodegenerative disorder, is thought to be involved in multiple iron-dependent mitochondrial pathways. In particular, frataxin plays an important role in the formation of iron-sulfur (Fe-S) clusters biogenesis.
  
  
  RESULTS
  We present data providing new insights into the interactions of mammalian frataxin with the Fe-S assembly complex by combining in vitro and in vivo approaches. Through immunoprecipitation experiments, we show that the main endogenous interactors of a recombinant mature human frataxin are ISCU, NFS1 and ISD11, the components of the core Fe-S assembly complex. Furthermore, using a heterologous expression system, we demonstrate that mammalian frataxin interacts with the preformed core complex, rather than with the individual components. The quaternary complex can be isolated in a stable form and has a molecular mass of ≈190 kDa. Finally, we demonstrate that the mature human FXN(81-210) form of frataxin is the essential functional form in vivo.
  
  
  CONCLUSIONS
  Our results suggest that the interaction of frataxin with the core ISCU/NFS1/ISD11 complex most likely defines the essential function of frataxin. Our results provide new elements important for further understanding the early steps of de novo Fe-S cluster biosynthesis.
authors.affiliation: Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Schmucker
authors.forename: Alain
authors.initials: A
authors.lastname: Martelli
authors.forename: Florent
authors.initials: F
authors.lastname: Colin
authors.forename: Adeline
authors.initials: A
authors.lastname: Page
authors.forename: Marie
authors.initials: M
authors.lastname: Wattenhofer-Donzé
authors.forename: Laurence
authors.initials: L
authors.lastname: Reutenauer
authors.forename: Hélène
authors.initials: H
authors.lastname: Puccio
mesh_terms: D013437:Carbon-Sulfur Lyases / Q000378:metabolism; D002470:Cell Survival; D006801:Humans; D033862:Iron-Binding Proteins / Q000502:physiology*; D035925:Iron-Regulatory Proteins / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes / Q000096:biosynthesis / Q000378:metabolism*; D011485:Protein Binding; D000096923:Frataxin
chemical_list: D013437:Carbon-Sulfur Lyases; D033862:Iron-Binding Proteins; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D000096923:Frataxin; C506160:ISCU protein, human; C544445:LYRM4 protein, human; C513492:NFS1 protein, human