Fig. 2.

Cellular iron transport and trafficking. A model of a generic cell is depicted. Cells can take up iron from TF (transferrin) as TBI (transferrin-bound iron) or from NTBI (non-transferrin-bound iron). Uptake of TBI is mediated by TFR1 (transferrin receptor 1)-mediated endocytosis as described in Section 2.2. NTBI uptake can be mediated, depending on the cell type, by SLC39A14, SLC39A8, DMT1, or LTCCs (L-type Ca²⁺ channels). Since most NTBI in plasma is present as Fe³⁺ species, and NTBI is transported as Fe²⁺, a reduction step, likely catalyzed by a reductase, precedes transport. Iron trafficking in the cytosol is mediated by PCBP1/2 (Poly (RC) Binding Protein 1/2), which delivers iron to ferritin, the iron storage protein, and several iron-containing enzymes (not shown). Iron is taken up into the mitochondrion via mitoferrin 1/2. Mobilization of iron from ferritin storage is mediated by NCOA4 (Nuclear Receptor Coactivator 4), which directs ferritin to the lysosome for degradation. Cellular iron export is mediated by FPN (ferroportin). Additional details are described in Section 2.2.