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

Numerous degenerative disorders are associated with elevated levels of pro-oxidants 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.