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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aconitate Hydratase / antagonists & inhibitors
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Aconitate Hydratase / metabolism*
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Animals
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Citric Acid / metabolism
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Citric Acid / pharmacology
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Dithiothreitol / metabolism
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Electron Spin Resonance Spectroscopy
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Enzyme Activation
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Ferrous Compounds / metabolism
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Frataxin
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Hydrogen Peroxide / pharmacology
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Iron / metabolism*
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Iron-Binding Proteins / metabolism*
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Male
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Mitochondria / metabolism*
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Mitochondria, Heart / metabolism*
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Molecular Chaperones / metabolism*
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Oxidation-Reduction
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Oxidative Stress
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Oxygen Consumption
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Rats
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Rats, Sprague-Dawley
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / metabolism
Substances
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Ferrous Compounds
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Iron-Binding Proteins
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Molecular Chaperones
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Saccharomyces cerevisiae Proteins
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Citric Acid
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Hydrogen Peroxide
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Iron
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Aconitate Hydratase
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Dithiothreitol