The transferrin cycle and iron uptake in rabbit reticulocytes. Pulse studies using 59Fe, 125I-labeled transferrin.
Rabbit reticulocytes were pulsed for 10 s with diferric 59Fe, 125I-labeled transferrin followed without further manipulation by a chase with unlabeled diferric transferrin. The 125I-transferrin and 59Fe were measured in different cell compartments as a function of time thereafter. Immediately after binding, transferrin entered a phase that lasted 60 s, characterized by a slow dissociation of transferrin into the extracellular medium. During this period, most of the iron originally present in transferrin is donated to the cell. The half-time of 59Fe release from transferrin was 43 s. After the initial 60 s, transferrin, now devoid of iron, is released into the medium. The whole transferrin cycle lasted about 4 min. The iron released from transferrin could be transiently found in the cell plasma membrane, the cytosol, and the mitochondria. All these compartments behaved like intermediates in the iron uptake process as their 59Fe content rose, reached a plateau, and gradually fell. Finally, the iron was incorporated into heme with a half-time of incorporation of 173 s. We conclude that the release of iron from transferrin is one of the fastest events occurring after the initial binding of transferrin. The limiting step in the entire process of iron delivery is the dissociation of apotransferrin from its receptor, a step which will enable the latter to undergo another cycle of transferrin binding.
D000818:Animals; D002453:Cell Cycle; D002462:Cell Membrane / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism*; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism*
D014168:Transferrin; D006418:Heme; D007501:Iron