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.. Fe-S cluster biosynthesis

AC Adam

Adeline Page

AL Bulteau

Alain Martelli

AR Correia

C Gellera

CL Tsai

DC Johnson

EC Raulfs

F Prischi

Florent Colin

Francesc Palau

G Duby

G Layer

H Koutnikova

H Li

H Puccio

HA O'Neill

Hélène Puccio

J Gerber

JD Cook

JM Berrisford

Laurence Reutenauer

M Nair

M Pandolfo

Marie Wattenhofer-Donzé

N Calmels

N Wiedemann

P Cavadini

PE Hart

R Lill

R Shi

S Adinolfi

S Leidgens

S Schmucker

Stéphane Schmucker

T Karlberg

T Wang

T Yoon

V Campuzano

Y He

Y Shan

PLoS ONE

English

PubMed

Schmucker Stéphane

Martelli Alain

Colin Florent

Page Adeline

Wattenhofer-Donzé Marie

Reutenauer Laurence

Puccio Hélène

Public Library of Science (PLOS)

Mammalian Frataxin: An Essential Function for Cellular Viability through an Interaction with a Preformed ISCU/NFS1/ISD11 Iron-Sulfur Assembly Complex

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. METHODOLOGY/PRINCIPAL FINDINGS: 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 approximately 190 kDa. Finally, we demonstrate that the mature human FXN(81-210) form of frataxin is the essential functional form in vivo. CONCLUSIONS/SIGNIFICANCE: 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

Schmucker, S. (Stéphane)

Martelli, A. (Alain)

Colin, F. (Florent)

Page, A. (A)

Wattenhofer-Donze, M. (Marie)

Reutenauer, L. (Laurence)

Puccio, H. (Hélène)

univOAK

Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron-sulfur assembly complex:

Crossref

A non-essential function for yeast frataxin in iron-sulfur cluster assembly.

An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1.

Antioxidant treatment of patients with Friedreich ataxia: four-year follow-up.

Assembly of human frataxin is a mechanism for detoxifying redox-active iron.

Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS.

Binding of yeast frataxin to the scaffold for Fe-S cluster biogenesis,

Conformational stability of human frataxin and effect of Friedreich’s ataxia-related mutations on protein folding.

Essential role of Isd11 in mitochondrial iron-sulfur cluster synthesis on Isu scaffold proteins.

Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity.

Frataxin gene point mutations in Italian Friedreich ataxia patients.

Frataxin interacts with Isu1 through a conserved tryptophan in its beta-sheet.

Frataxin-mediated iron delivery to ferrochelatase in the final step of heme biosynthesis.

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Function and biogenesis of iron-sulphur proteins.

Human frataxin is an allosteric switch that activates the Fe-S cluster biosynthetic complex.

Human frataxin maintains mitochondrial iron homeostasis in Saccharomyces cerevisiae.

In vivo iron-sulfur cluster formation.

Iron-sulfur cluster biosynthesis: characterization of Escherichia coli CYaY as an iron donor for the assembly of [2Fe-2S] clusters in the scaffold IscU.

Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe-2S] clusters in ISU-type proteins.

Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase.

Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones.

Monomeric yeast frataxin is an iron-binding protein.

Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits.

Multicellular models of Friedreich ataxia.

Oligomeric yeast frataxin drives assembly of core machinery for mitochondrial iron-sulfur cluster synthesis.

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Structural bases for the interaction of frataxin with the central components of iron-sulphur cluster assembly.

Structural basis for Fe-S cluster assembly and tRNA thiolation mediated by IscS proteinprotein interactions.

Structural basis for the mechanism of respiratory complex I.

Structure, function, and formation of biological iron-sulfur clusters.

The first cellular models based on frataxin missense mutations that reproduce spontaneously the defects associated with Friedreich ataxia.

The in vivo mitochondrial two-step maturation of human frataxin.

The Nfs1 interacting protein Isd11 has an essential role in Fe/S cluster biogenesis in mitochondria.

The structures of frataxin oligomers reveal the mechanism for the delivery and detoxification of iron.

Understanding the molecular mechanisms of Friedreich’s ataxia to develop therapeutic approaches.

Yeast frataxin solution structure, iron binding, and ferrochelatase interaction.

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Mammalian Frataxin: An Essential Function for Cellular Viability through an Interaction with a Preformed ISCU/NFS1/ISD11 Iron-Sulfur Assembly Complex

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