Fig. 6

Model of Iron Release Regulation. In our proposed model, in areas that have higher ratios of apo- to holo-Tf (A), apo-Tf binds to Heph in order to accept the exported free iron and further stimulates iron release through Fpn. Alternatively, areas of lower ratios of apo- to holo-Tf (B), excessive holo-Tf binds to Fpn to facilitate the ubiquitination, internalization, and degradation of Fpn, and thus suppressing iron release through Fpn. In environments of inflammation or high iron levels, hepcidin production is upregulated (C). Hepcidin binds to Fpn and rapidly triggers Fpn’s internalization and abruptly stops free iron release