Schematic figure of key similarities and differences between WT and LysM-Atg5^−/− mice. (A) WT mice. Erythrocytes are phagocytosed by macrophages. Macrophages efficiently recycle phagocytosed iron to transferrin in the circulation, and with the help of autophagy (ATG), the excess iron is stored in hemosiderin. A small amount of iron uptake by enterocytes is released from enterocytes; most is stored in ferritin. Tranferrin-bound iron is carried to BM. Iron is incorporated into newly formed erythrocytes within the BM. Hepcidin produced from hepatocytes and macrophages controls cell iron release. (B) LysM-Atg5^−/− mice. Erythrocytes are phagocytosed by macrophages. Macrophages efficiently recycle phagocytosed iron to transferrin in the circulation, but without functional ATG, ferroportin from RBCs cannot be sufficiently degraded, and the excess iron cannot be stored in hemosiderin. High iron release from macrophages decreases hepcidin expression. A large amount of iron is released from macrophages and absorbed from enterocytes. Tranferrin-bound iron is carried in excess to BM and extramedullary sites of erythropoiesis. Iron is incorporated into an excess of newly formed erythrocytes. Dashed lines indicate iron transit.