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Science 9 July 2004:
Vol. 305. no. 5681, pp. 242 - 245
DOI: 10.1126/science.1098991
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Reports

Frataxin Acts as an Iron Chaperone Protein to Modulate Mitochondrial Aconitase Activity

Anne-Laure Bulteau,1 Heather A. O'Neill,2 Mary Claire Kennedy,3 Masao Ikeda-Saito,4 Grazia Isaya,2 Luke I. Szweda1*

Numerous degenerative disorders are associated with elevated levels of prooxidants and declines in mitochondrial aconitase activity. Deficiency in the mitochondrial iron-binding protein frataxin results in diminished activity of various mitochondrial iron-sulfur proteins including aconitase. We found that aconitase can undergo reversible citrate-dependent modulation in activity in response to pro-oxidants. Frataxin interacted with aconitase in a citrate-dependent fashion, reduced the level of oxidant-induced inactivation, and converted inactive [3Fe-4S]1+ enzyme to the active [4Fe-4S]2+ form of the protein. Thus, frataxin is an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation.

1 Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA.
2 Departments of Pediatric and Adolescent Medicine and Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA.
3 Department of Chemistry, Gannon University, Erie, PA, USA.
4 Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira, Aoba-ku, Sendai 980-8577, Japan.

* To whom correspondence should be addressed. E-mail: lxs54{at}po.cwru.edu

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