title: Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Bulteau
authors.forename: Heather A
authors.initials: HA
authors.lastname: O'Neill
authors.forename: Mary Claire
authors.initials: MC
authors.lastname: Kennedy
authors.forename: Masao
authors.initials: M
authors.lastname: Ikeda-Saito
authors.forename: Grazia
authors.initials: G
authors.lastname: Isaya
authors.forename: Luke I
authors.initials: LI
authors.lastname: Szweda
mesh_terms: D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D019343:Citric Acid / Q000378:metabolism / Q000494:pharmacology; D004229:Dithiothreitol / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation; D005296:Ferrous Compounds / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D000096923:Frataxin
chemical_list: D000154:Aconitate Hydratase; D019343:Citric Acid; D004229:Dithiothreitol; D005296:Ferrous Compounds; D006861:Hydrogen Peroxide; D007501:Iron; D033862:Iron-Binding Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D000096923:Frataxin