Ferritin and iron uptake by reticulocytes

S ummary . The uptake of liver ferritin labelled with 125 I or 59 Fe by guinea‐pig reticulocytes has been studied to investigate the characteristics of the uptake process, compare it with transferrin uptake and determine whether ferritin‐iron is utilized by the cells in haem synthesis. The results confirmed that guinea‐pig reticulocytes, but not mature erythrocytes, take up liver ferritin by a saturable, time‐ and temperature‐dependent process. Up to 70% of the iron taken up by the cells was utilized in haem synthesis and competed directly with iron derived from transferrin. Scatchard analysis of the binding parameters indicated that 30–130 × 10 3 ferritin molecules were bound per cell to high affinity specific membrane receptors ( K a : 1·77 × 10 7 M −1 ). In contrast, rat took up much less ferritin than guinea‐pig reticulocytes and the process was entirely non‐specific. Release experiments with guinea‐pig reticulocytes at 37°C showed that a maximum of about 70% of the cell‐associated 125 I‐ferritin was released from the cells of which up to 15% was trichloroacetic acid‐soluble. We suggest that ferritin uptake by guinea‐pig reticulocytes involves receptor‐mediated endocytosis. The endocytotic vesicle fuses with a lysosome, iron is removed from the protein and enters a cytosolic pool in which it competes directly with transferrin‐derived iron to provide iron for mitochondrial haem synthesis. Some of the ferritin is catabolized and the rest is returned to the extracellular medium during membrane recycling.