Aconitases: Non-redox Iron–Sulfur Proteins Sensitive to Reactive Species

ConspectusMammalian aconitases (mitochondrial and cytosolic isoenzymes) are unique iron–sulfur cluster-containing proteins in which the metallic center participates in the catalysis of a non-redox reaction. Within the cubane iron–sulfur cluster of aconitases only three of the four iron ions have cysteine thiolate ligands; the fourth iron ion (Feα) is solvent exposed within the active-site pocket and bound to oxygen atoms from either water or substrates to be dehydrated. The catalyzed reaction is the reversible isomerization of citrate to isocitrate with an intermediate metabolite, cis-aconitate. The cytosolic isoform of aconitase is a moonlighting enzyme; when intracellular iron is scarce, the complete disassembly of the iron–sulfur cluster occurs and apo-aconitase acquires the function of an iron responsive protein and regulates the translation of proteins involved in iron metabolism.In the late 1980s and during the 1990s, cumulative experimental evidence pointed out that aconitases are main targets of r...