Frataxin is a mitochondrial protein that is defective in Friedreich's ataxia resulting in iron accumulation and an environment prone to Fenton reactions. We report that frataxin is susceptible to carbonylation and nitration modifications in residues from the beta-sheet surface (Tyr143, Tyr174, Tyr205 and Trp155). Frataxin functions are not significantly affected: frataxin-mediated protection ag...

The biosynthesis of iron sulfur (Fe-S) clusters in Bacillus subtilis is mediated by a SUF-type gene cluster, consisting of the cysteine desulfurase SufS, the scaffold protein SufU, and the putative chaperone complex SufB/SufC/SufD. Here, we present the high-resolution crystal structure of the SufS homodimer in its product-bound state (i.e., in complex with pyrodoxal-5'-phosphate, alanine, Cys36...

Frataxin is the protein responsible for the genetically-inherited neurodegenerative disease Friedreich's ataxia caused by partial silencing of the protein and loss of function. Although the frataxin function is not yet entirely clear, it has been associated to the machine that builds iron-sulfur clusters, essential prosthetic groups involved in several processes and is strongly conserved in org...

Frataxin protein controls iron availability in mitochondria and reduced levels lead to the human disease, Friedreich's ataxia (FRDA). The molecular aspects of disease progression are not well understood. We developed a highly regulatable promoter system for expressing frataxin in yeast to address the consequences of chronically reduced amounts of this protein. Shutting off the promoter resulted...

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The N-terminal stretch of human frataxin (hFXN) intermediate (residues 42-80) is not conserved throughout evolution and, under defined experimental conditions, behaves as a random-coil. Overexpression of hFXN56-210 in Escherichia coli yields a multimer, whereas the mature form of hFXN (hFXN81-210) is monomeric. Thus, cumulative experimental evidence points to the N-terminal moiety as an essenti...

Background: Defects in the protein frataxin give rise to Friedreich ataxia. Results: A new Friedreich ataxia model using fission yeast has been generated, and its phenotype and proteome characterized. Conclusion: Frataxin absence triggers a complete iron starvation program, sufficient to generate all the associated respiratory defects. Significance: Our new model system may contribute to deciph...

What are the structural implications for iron binding by frataxin, the mitochondrial protein whose decreased expression results in Friedreich's ataxia? Though frataxin has been shown to be essential for proper handling of iron within mitochondria (e.g. for iron-sulfur cluster and haem biosynthesis), its exact molecular function remains unclear. In this issue of the Biochemical Journal, Correia ...

Expansion of an unstable GAA.TTC repeat in the first intron of the FXN gene causes Friedreich ataxia by reducing frataxin expression. Deficiency of frataxin, an essential mitochondrial protein, leads to progressive neurodegeneration and cardiomyopathy. The degree of frataxin reduction correlates with GAA.TTC tract length, but the mechanism of reduction remains controversial. Here we show that t...

Friedreich ataxia is caused by decreased levels of frataxin, a mitochondrial acidic protein that is assumed to act as chaperone in the assembly of Fe-S clusters on the scaffold Isu protein. Frataxin has the in vitro capacity to form iron-loaded multimers, which also suggests an iron storage function. It has been reported that alanine substitution of residues in an acidic ridge of yeast frataxin...