Fig. 7: A schematic model depicting ZIP13’s role in iron homeostasis regulation.

ZIP13 plays a critical role in gating an iron flow route that affects iron homeostasis in several major cellular compartments, including the cytosol, the ER/Golgi, the lysosome as well as the mitochondrion. a Under normal conditions, ZIP13 redistributes or partitions the cytosolic iron. It transports a part of the cytosolic iron into the ER/Golgi, where it traffics further to the lysosome and mitochondria. b When ZIP13 loses its function, this iron trafficking route is blocked. More iron is accumulated in the cytosol and less in the ER/Golgi, lysosome, and mitochondrion. c When ZIP13 is more active, more cytosolic iron is diverted to this pathway, leading to more iron in the corresponding compartments and less iron in the cytosol. Green: ZIP13; yellow: Fe²⁺; orange: Fe³⁺; pink: FPN1.