Skip Navigation


Human Molecular Genetics Advance Access originally published online on June 27, 2007
Human Molecular Genetics 2007 16(22):2651-2658; doi:10.1093/hmg/ddm163
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
16/22/2651    most recent
ddm163v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Martelli, A.
Right arrow Articles by Puccio, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martelli, A.
Right arrow Articles by Puccio, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Alain Martelli1,{dagger}, Marie Wattenhofer-Donzé1,5,{dagger}, Stéphane Schmucker1,4, Samuel Bouvet1, Laurence Reutenauer1,3 and Hélène Puccio1,2,3,4,5,*

1 IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), 1 rue Laurent Fries BP 10142, Illkirch F-67400, France, 2 Inserm, U596, Illkirch F-67400, France, 3 CNRS, UMR7104, Illkirch F-67400, France, 4 Université Louis Pasteur, Strasbourg F-67000, France and 5 Collège de France, Chaire de Génétique Humaine, Illkirch F-67400, France

* To whom correspondence should be addressed. Tel: +33 388653264; Fax: +33 388653246; Email: hpuccio{at}titus.igbmc.u-strasbg.fr

Received May 28, 2007; Revised June 21, 2007; Accepted June 21, 2007

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.

{dagger} The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.