Iron uptake in reticulocytes. Inhibition mediated by the ionophores monensin and nigerisin.

The lipophilic carboxylic ionophores monensin and nigerisin reversibly blocked iron uptake by erythroid cells. At low concentrations of ionophores (0.25-0.5 microM), the disruption of the compartment in which iron is released affected minimally the release of iron from transferrin but effectively inhibited iron uptake. Iron released from transferrin was extruded from the cell synchronously with but not bound to transferrin. The compartment disrupted by the ionophores, and in which iron is released from transferrin, is apparently contiguous to the extracellular medium. Contiguity was assessed by determining the effect of extracellular Na+ and K+ on the activity of the ionophores. The above data fit a model of iron uptake in which iron is released from transferrin in an acidic compartment in immediate contiguity with the cell plasma membrane. Iron is then bound by its membrane acceptor and is translocated to the cytosolic side of the plasma membrane. At submicromolar concentrations, the ionophores monensin and nigerisin produce a small increase in the pH of the acidic compartment. The pH change, which is not sufficient to block the release of iron from transferrin, is enough to block the binding of released iron to its acceptor in the plasma membrane, thus producing inhibition of iron uptake.