Cellular Ferritin Uptake: A Highly Regulated Pathway for Iron Assimilation in Human Erythroid Precursor Cells
Normal erythropoiesis requires the regulated delivery of iron to differentiating erythroid precursor cells. The delivery of iron to the cells, in vivo, is ascribed, traditionally, exclusively to the iron transport protein transferrin (Tf)1. Ferritin is regarded mainly as an iron detoxifying and storage protein2, its synthesis is down-regulated in iron depleted cells and up-regulated when cellular iron is in abundance. Ferritin is a multimeric, globular protein composed of 24 subunits surrounding a central core of up to 4500 iron atoms The protein shell can be composed of two different subunits a heavy, (H type) and a light, (L type). Isoferritins rich in H-type subunits have a lower Pi (Acidic isoferritins) than isoferritins rich in L type subunits5-6. Other functions, than its accepted role has been assigned to ferritin. Ferritin has been accredited however, as a cytosolic iron transport intermediate in human reticulocytes7 and as such as a possible donor of iron for heme in both, human7 and mouse reticulocytes8. Isolated rat mitochondria could use ferritin iron for the ferrochelatase reaction. In addition Speyer and Fielding argue that ferritin is an obligatory intermediate for iron transport between the reticulocyte plasma membrane and the site of iron incorporation into heme. Biochemical and electron micrograph studies on guinea-pig reticulocytes implicate the presence of specific receptors for ferritin on the cell membrane pp10-11 . Ferritin binding to guinea-pig reticulocytes and its subsequent internalization has been demonstrated by Blight and Morgan 12. They used liver ferritin that is rich in L type subunits and therefore mostly basic in nature. These studies were done with circulating reticulocytes that represent the penultimate stage of erythroid maturation. At this stage cellular ferritin synthesis has already been diminished and the ferritin utilized13. The view of ferritin as an active metabolic intermediate in erythrocyte precursors gives significance to the old observations of Gabusda and Pearson who showed that erythroblast ferritin is metabolically and structurally distinct from reticuloendothelial ferritin. They proposed erythroblast ferritin as an intermediate en route to heme synthesis.
KeywordsErythroid Cell Erythroid Precursor Heme Synthesis Iron Responsive Element Liver Ferritin
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