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Open Access Highly Accessed Research article

Deferiprone targets aconitase: Implication for Friedreich's ataxia treatment

Sergio Goncalves, Vincent Paupe, Emmanuel P Dassa and Pierre Rustin*

Author Affiliations

Inserm, U676, Hôpital Robert Debré, Paris, F-75019 France and Université Paris 7, Faculté de Médecine Denis Diderot, IFR02, Paris, France

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BMC Neurology 2008, 8:20  doi:10.1186/1471-2377-8-20

Published: 16 June 2008

Abstract

Background

Friedreich ataxia is a neurological disease originating from an iron-sulfur cluster enzyme deficiency due to impaired iron handling in the mitochondrion, aconitase being particularly affected. As a mean to counteract disease progression, it has been suggested to chelate free mitochondrial iron. Recent years have witnessed a renewed interest in this strategy because of availability of deferiprone, a chelator preferentially targeting mitochondrial iron.

Method

Control and Friedreich's ataxia patient cultured skin fibroblasts, frataxin-depleted neuroblastoma-derived cells (SK-N-AS) were studied for their response to iron chelation, with a particular attention paid to iron-sensitive aconitase activity.

Results

We found that a direct consequence of chelating mitochondrial free iron in various cell systems is a concentration and time dependent loss of aconitase activity. Impairing aconitase activity was shown to precede decreased cell proliferation.

Conclusion

We conclude that, if chelating excessive mitochondrial iron may be beneficial at some stage of the disease, great attention should be paid to not fully deplete mitochondrial iron store in order to avoid undesirable consequences.