Figure 2.
Transferrin (Tf) and transferrin receptor (TfR) function in iron homeostasis. Tf binds iron entering circulation via dietary absorption, iron recycling of red blood cells, or release from liver stores. These export pathways are regulated by the hormone hepcidin, which responds to iron saturation sensed by Tf–TfR through the hereditary hemochromatosis protein HFE. If there is iron surplus, Tf binding competes with HFE for association with TfR1, enabling it to bind TfR2 and participate in signaling hepcidin upregulation. Under these conditions, TfR1 mediates iron delivery, ultimately targeting the nutrient for metabolism or storage. When Tf saturation becomes reduced under low iron conditions, TfR2 is destabilized, and endocytic delivery is adjusted to meet functional demands.