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. Author manuscript; available in PMC: 2022 Dec 1.
Published in final edited form as: Ageing Res Rev. 2021 Nov 9;72:101510. doi: 10.1016/j.arr.2021.101510

Fig. 3. Important regulators involved in cellular iron homeostasis.

Fig. 3.

Non-heme iron can enter the cell in two forms: transferrin bound (TFB) and non-transferrin bound (aka NTBI). Ferrous iron or NTBI enters the cell through DMT1. Ferric iron is reduced to ferrous iron by DcytB, whereas ferrous iron is oxidized into ferric iron by the multicopper ferroxidases ceruloplasmin, hephaestin and HephL1. Ferric iron binds to transferrin that in turn binds to the transferrin receptor and gets internalized into the cell via endocytosis. Inside the internalized vesicles, iron is released and transformed into ferrous iron by STEAP3. Ferrous iron will then be exported out of the vesicle and into the cytoplasm by DMT1. Ferrous iron in the cytoplasm constitutes the labile iron pool (LIP), and it can be exported out of the cell by ferroportin, stored in the cell by ferritin, or utilized in different cellular processes. As for heme, it is synthesized in the mitochondria and can be exported to the outside of the cell by FLVCR1. Once in the cytoplasm, heme is cleaved by heme oxygenase (HO1) to release ferrous iron.