Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity.
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.
Bulteau
Anne-Laure
AL
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA.
O'Neill
Heather A
HA
Kennedy
Mary Claire
MC
Ikeda-Saito
Masao
M
Isaya
Grazia
G
Szweda
Luke I
LI
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
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