Yeast frataxin sequentially chaperones and stores iron by coupling protein assembly with iron oxidation

摘要: We have investigated the mechanism of frataxin, a conserved mitochondrial protein involved in iron metabolism and neurodegenerative disease. Previous studies revealed that yeast frataxin homologue (mYfh1p) is activated by Fe(II) presence O2 assembles stepwise into 48-subunit multimer (α48) sequesters >2000 atoms 2–4-nm cores structurally similar to ferritin cores. Here we show mYfh1p assembly driven two sequential oxidation reactions: A ferroxidase reaction catalyzed induces first step (α → α3), followed slower autoxidation promotes higher order oligomers yielding α48. Depending on ionic environment, associated with accumulation 50–75 Fe(II)/subunit. Initially, this loosely bound can be readily mobilized chelators or made available enzyme ferrochelatase synthesize heme. Transfer mYfh1p-bound occurs citrate, physiologic ferrous chelator, suggesting transfer involves an intermolecular interaction. If not transferred ligand, oxidation, mineralization proceed completion, Fe(III) becomes progressively less accessible, stable iron-protein complex formed. Iron oxidation-driven novel which function as chaperone store.