Ferroptosis, a new form of cell death defined after radiation exposure

Ferroptosis is an iron-dependent form of regulated cell death, driven by excessive lipid peroxidation and/or inactivation/depletion of protective molecules against lipid peroxidation. Ionizing radiation can induce ferroptosis in both normal tissues and tumor cells. Here, we reviewed the findings of ionizing radiation-induced ferroptosis.

Ionizing radiation induces an increase in hydroxyl radicals, free iron, and lipid metabolic enzymes, which subsequently synergistically initiate a high level of lipid peroxidation, making ionizing radiation an exogenous inducer of ferroptosis. In addition, ferroptosis may be the primary form of cell death in the bone marrow under hematopoietic acute radiation syndrome. Ionizing radiation can also induce changes in iron metabolism, which may be a target for regulating ferroptosis. Finally, ionizing radiation-induced ferroptosis initiates from the cytoplasm and ends on the membrane, and is independent of DNA damage.