Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity

Anne Laure Bulteau, Heather A. O'Neill, Mary Claire Kennedy, Masao Ikeda-Saito, Grazia Isaya, Luke I. Szweda

Research output: Contribution to journalArticle

293 Citations (Scopus)

Abstract

Numerous degenerative disorders are associated with elevated levels of pro-oxidants and declines in mitochondriat aconitase activity. Deficiency in the mitochondrial iron-binding protein frataxin results in diminished activity of various mitochondriat iron-sutfur 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.

Original languageEnglish (US)
Pages (from-to)242-245
Number of pages4
JournalScience
Volume305
Issue number5681
DOIs
StatePublished - Jul 9 2004

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Aconitate Hydratase
Iron
Proteins
Citric Acid
Reactive Oxygen Species
Iron-Binding Proteins
Mitochondrial Proteins
Enzymes
Oxidants
frataxin

ASJC Scopus subject areas

  • General

Cite this

Bulteau, A. L., O'Neill, H. A., Kennedy, M. C., Ikeda-Saito, M., Isaya, G., & Szweda, L. I. (2004). Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. Science, 305(5681), 242-245. https://doi.org/10.1126/science.1098991

Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. / Bulteau, Anne Laure; O'Neill, Heather A.; Kennedy, Mary Claire; Ikeda-Saito, Masao; Isaya, Grazia; Szweda, Luke I.

In: Science, Vol. 305, No. 5681, 09.07.2004, p. 242-245.

Research output: Contribution to journalArticle

Bulteau, AL, O'Neill, HA, Kennedy, MC, Ikeda-Saito, M, Isaya, G & Szweda, LI 2004, 'Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity', Science, vol. 305, no. 5681, pp. 242-245. https://doi.org/10.1126/science.1098991
Bulteau, Anne Laure ; O'Neill, Heather A. ; Kennedy, Mary Claire ; Ikeda-Saito, Masao ; Isaya, Grazia ; Szweda, Luke I. / Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. In: Science. 2004 ; Vol. 305, No. 5681. pp. 242-245.
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