Cellular iron handling. The 4 general mechanisms of cellular iron handling are shown. Iron is taken up through the endosomal cycle of TFR1 by all cells, but also by DMT1 (enterocytes) or RBC breakdown (macrophages). Within the cell, the labile iron pool (LIP) is used for metabolic needs. Most iron is transported to mitochondria to be used for iron sulfur cluster and heme biogenesis. In the cytosol, excess iron is stored in ferritin, a molecule that is also secreted into the circulation. Excess iron can also be exported through FPN. Used with permission from Hentze et al.¹