Journal Article

Frataxin is essential for extramitochondrial Fe–S cluster proteins in mammalian tissues

Alain Martelli, Marie Wattenhofer-Donzé, Stéphane Schmucker, Samuel Bouvet, Laurence Reutenauer and Hélène Puccio

in Human Molecular Genetics

Volume 16, issue 22, pages 2651-2658
Published in print November 2007 | ISSN: 0964-6906
Published online June 2007 | e-ISSN: 1460-2083 | DOI:
Frataxin is essential for extramitochondrial Fe–S cluster proteins in mammalian tissues

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Friedreich ataxia, the most common recessive ataxia, is caused by the deficiency of the mitochondrial protein frataxin (Fxn), an iron chaperone involved in the assembly of Fe–S clusters (ISC). In yeast, mitochondria play a central role for all Fe–S proteins, independently of their subcellular localization. In mammalian cells, this central role of mitochondria remains controversial as an independent cytosolic ISC assembly machinery has been suggested. In the present work, we show that three extramitochondrial Fe–S proteins (xanthine oxido-reductase, glutamine phosphoribosylpyrophosphate amidotransferase and Nth1) are affected in Fxn-deleted mouse tissues. Furthermore, we show that Fxn is strictly localized to the mitochondria, excluding the presence of a cytosolic pool of Fxn in normal adult tissues. Together, these results demonstrate that in mammals, Fxn and mitochondria play a cardinal role in the maturation of extramitochondrial Fe–S proteins. The Fe–S scaffold protein IscU progressively decreases in Fxn-deleted tissues, further contributing to the impairment of Fe–S proteins. These results thus provide new cellular pathways that may contribute to molecular mechanisms of the disease.

Journal Article.  5162 words.  Illustrated.

Subjects: Genetics and Genomics

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