Fig. 9.

Proposed mechanism for the fate of iron extracted from ferritin in the lysosome. (A) Ferritin is targeted to the lysosome by autophagy under iron-depleted conditions in primary cells. Iron released from ferritin in the lysosome is transported to the cytoplasm and used by cells because ferritin production is suppressed under iron-depleted conditions in primary cells. This may also be the case in cancer-derived cells. (B) Ferritin is targeted to the lysosome by an autophagy-independent pathway that is 3-MA sensitive. In primary cells, iron released from ferritin in the lysosome is transported to the cytoplasm and sequestered in newly synthesized ferritin to prevent iron toxicity under iron-replete conditions. In cancer-derived cells, ferritin is not degraded, and excess iron is stably and safely stored by ferritin under iron-rich conditions.