Figure 2.

Iron chelation and redeployment. The redeployment strategy leans on permeant chelators (CH) (I) that gain access to cells (normal or Fe-overloaded), (II) chelate labile cell iron and, following egress from cells into plasma, transfer (III) the chelated Fe to circulating apotransferrin Tf to form TfFe (IV), which in turn re-deploys the metal to Fe-deficient cells (V) in a conservative cycle. The various steps in the chelation-redeployment cycle have been demonstrated preclinically with the bidentate Fe (III) chelator deferiprone (DFP) (Sohn et al., 2011; Kakhlon et al., 2010; Fleming and Ponka, 2012). Given that DFP-Fe chelates donate metal to cell or plasma iron-acceptors (e.g., apo-Tf), the modus operandii of the chelators resembles siderophores or chaperons that redistribute iron across cells and their compartments.