Figure 4
Mechanism of mitochondrial aconitase inactivation. Mitochondrial aconitase is a tricarboxylic acid (TCA) cycle enzyme that catalyzes the conversion of citrate to isocitrate. It contains an iron-sulfur cluster ([4Fe-4S]) in its active site that is inactivated by superoxide (O•−) produced in close proximity as a byproduct of the electron transport chain. This results in the release of a Fe+2 and a molecule of hydrogen peroxide (H2O2), which, through the Fenton reaction, can react to produce a hydroxyl radical (•OH). The glutathione redox capacity (GSH/GSSG) will decrease as a result of the elevated free-radical production and will allow more superoxide inactivation of aconitase, creating a self-amplifying cycle if left unresolved.
