Fig. 11. Proposed mechanism for IRP1 interaction with the ER and Golgi membrane fractions. This schematic demonstrates the intracellular distributions of IRP1 discovered in this study. IRP1 is found in Golgi membranes in addition to the cytosol. Under conditions of low iron and in cells in culture, IRP1 is also found in the ER membranes. We propose that under low iron conditions IRP1 is incorporated into the ER membrane by a hydrophobic tail immediately after translation. Within the ER, IRP1 can serve to further stabilize transferrin receptor (TfR) mRNA by binding to IREs that were not bound in the cytoplasm. Once the TfR mRNA has been translated, the IRPs in the ER membrane move to the Golgi membrane where they can receive an Fe-S cluster. The acquisition of an Fe-S cluster is not required for IRP1 to be released from the Golgi membrane to the cytosol or be recycled to the ER membrane.