Ferritin and iron uptake by reticulocytes.
The uptake of liver ferritin labelled with 125I or 59Fe 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 X 10(3) ferritin molecules were bound per cell to high affinity specific membrane receptors (Ka: 1.77 X 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 degrees C showed that a maximum of about 70% of the cell-associated 125I-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.
D000818:Animals; D005293:Ferritins / Q000378:metabolism*; D006168:Guinea Pigs; D006418:Heme / Q000378:metabolism; D007457:Iodine Radioisotopes; D007501:Iron / Q000378:metabolism*; D007504:Iron Radioisotopes; D007700:Kinetics; D008297:Male; D011506:Proteins / Q000378:metabolism; D051381:Rats; D012156:Reticulocytes / Q000378:metabolism*; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism
D007457:Iodine Radioisotopes; D007504:Iron Radioisotopes; D011506:Proteins; D014168:Transferrin; D006418:Heme; D005293:Ferritins; D007501:Iron