Cytosolic iron donor

Although there is some experimental evidence which points to a binding of iron ions by specific cytosolic proteins (see Cytosolic Iron Donor, below), these proteins, with the exception of transferrin, are available only in minute quantities, and the nature and extent of iron-protein interactions are poorly understood. Therefore, a number of nonprotein iron chelates have been studied as possible model donor complexes (Table I). Because of the high stability constants of, for example, the Fe(II)/Fe(III)-8-hydroxyquinoline and Fe(III)-ADP complexes (20), these iron-chelate complexes are unfavorable as iron donors, and in fact no energy-dependent uptake of iron has been detected using these complexes (21, 23). 

While most soluble cellular iron is associated with an ill-defined labile iron pool, much of the iron that is used by the cell is found in the form of specific iron cofactors especially as iron-sulfur clusters and hemes. The biosynthesis of iron-sulfur centers has only come of age within the past decade following the characterization of operons encoding cluster assembly genes by Dean and coworkers 4), In eukaryotes, homologous proteins are nuclear transcribed. While predominantly localized within the mitochondrial matrix, one group has reported cytosolic ISU (cluster assembly protein) and NFS (S-donor protein) in human cell lines (5). Alternative cytoplasmic cluster maturation proteins have also been proposed (6). Whether the cytosolic components represent an independent assembly apparatus is unclear, nevertheless, both models support a role for ISU-mediated assembly of [2Fe-2S] building blocks prior to delivery to a target protein (7-P). 

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