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Terminal differentiation of erythropoietic progenitors requires the rapid accumulation of large amounts of iron, which is transported to the mitochondria, where it is incorporated into heme. Ferritin is the sole site of iron storage present in the cytosol. Yet the role of iron accumulation into ferritin in the context of red cell development had not been clearly defined. Early studies indicated that at the onset of terminal differentiation, iron initially accumulates in ferritin and precedes heme synthesis. Whether this accumulation is physiologically important for red cell development was unclear until recent studies defined an obligatory pathway of iron flux through ferritin.

The flux of iron through ferritin in erythrocyte development