Figure 2.

Mechanisms of iron metabolism in ferroptosis. Fe³⁺ can couple to transferrin and enter the intercellular milieu mediated by TfR1. Transferrin can be recycled and exported extracellularly and blocked by HSPB1. Fe³⁺ is reduced to Fe²⁺ by DMT1 in endosomes, and Fe²⁺ can be transported into the cytoplasm. Fe²⁺ can be released from ferritin through NCOA4-mediated ferritin phagocytosis, and part of Fe²⁺ can be exported outside the cell and oxidized by FPN. In addition, DOX can also induce ferroptosis. Cardiac output of DOX activates the Keap1/Nrf2 pathway, and Nrf2 further activates the downstream protein Hmox1 and prompts it to oxidize heme and release iron, leading to ferroptosis.