Regulation of Intracellular Iron Metabolism in Human Erythroid Precursors by Internalized Extracellular Ferritin

Human erythroid precursors grown in culture possess mem-brane receptors that bind and internalize acid isoferritin. These receptors are regulated by the iron status of the cell, implying that ferritin iron uptake may represent a normal physiologic pathway. The present studies describe the fate of internalized ferritin, the mechanisms involved in the release of its iron, and the recognition of this iron by the cell. Normal human erythroid precursors were grown in a 2-phase liquid culture that supports the proliferation, differentiation, and maturation of erythroid precursors. At the stage of polychromatic normoblasts, cells were briefly incubated with 59Fe- and/or 125I-labeled acid isoferritin and chased. The 125I-labeled ferritin protein was rapidly degraded and only 50 % of the label remained in intact ferritin protein after 3 to 4 hours. In parallel, 59Fe decreased in ferritin and increased i