Receptor-independent uptake of transferrin-bound iron by reticulocytes

Under physiological conditions the uptake of transferrin-bound iron by reticulocytes involves transferrin binding to membrane receptors followed by endocytosis, release of iron from the transferrin within endosomes, and recycling of apotransferrin to the cell surface. However, as shown in the present work, iron uptake and incorporation into heme will also occur if the cells are incubated in low-ionic-strength media such as isotonic sucrose. This process has a pH optimum of 5.9, is not inhibited by inactivation of the transferrin receptors, and does not involve transferrin endocytosis, but is inhibited by addition of various salts, ferricyanide, and low concentrations of ferric iron chelators, including apotransferrin, to the incubation medium. Iron uptake is temperature dependent, has a high activation energy and is inhibited by a variety of metabolic inhibitors. It is also saturable with an apparent Km of approximately 0.2 microM transferrin-Fe. It is concluded that under these incubation conditions iron is released from transferrin at the external surface of the cell and is transported into the cell by a facilitated, possibly active, transport process. This may occur via the iron carrier which normally functions in the membrane lining of endosomes. Reduction of the iron to the ferrous state is probably necessary for its transport into the cell.