Acidic residues of yeast frataxin have an essential role in Fe-S cluster assembly

• Published in: EMBO reports 2007-02, Vol.8 (2), p.194-199
• Main Authors: Foury, Françoise, Pastore, Annalisa, Trincal, Mathieu
• Format: Article
• Language: English
• Subjects: acidic residue; acidic ridge; Acids; Adrenodoxin - metabolism; Amino Acid Sequence; Amino Acid Substitution - genetics; Cloning, Molecular; EMBO24; Fe-S cluster; Frataxin; Iron; Iron - metabolism; Iron-Binding Proteins - genetics; Iron-Binding Proteins - metabolism; Iron-Sulfur Proteins - biosynthesis; Isu1; mitochondria; Mitochondria - metabolism; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Mutation - genetics; Oligonucleotides; Proteins; Residues; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Scientific Report; Yeast; Yeasts
• ISSN: 1469-221X; 1469-3178; 1469-221X
• DOI: 10.1038/sj.embor.7400881

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 (Yfh1) elicits loss of iron binding in vitro but has no effect on Fe–S cluster synthesis in vivo . Here, we show that a marked change in the electrostatic properties of a specific region of Yfh1 surface—by substituting two or four acidic residues by lysine or alanine, respectively—impairs Fe–S cluster assembly, weakens the interaction between Yfh1 and Isu1, and increases oxidative damage. Therefore, the acidic ridge is essential for the Yfh1 function and is likely to be involved in iron‐mediated protein–protein interactions.