Fig. 8: The general mechanism of ferroptosis.
From: Ferroptosis is involved in PGPS-induced otitis media in C57BL/6 mice
After Fe3+ enters the cell membrane through transferrin-1, it is converted into Fe2+. After a series of processes in the Fenton reaction, it finally affects the expression of GPX4 and ACSL4, leading to lipid peroxidation and ferroptosis. The arachidonic acid the oxidation reaction produces subsequently produces prostaglandins under the action of the Cox2, finally leading to inflammation. DFO is a chelating agent of iron. After DFO enters the cells, it causes the reduction of iron, thereby inhibiting the Fenton reaction and ultimately resulting in up-regulation of GPX4 and down-regulation of ACSL4, the inhibition of lipid peroxidation, and the inhibition of ferroptosis and inflammation. Lip-1 and Fer-1 are produced by direct inhibition of cellular lipid peroxidation, which leads to inhibition of ferroptosis and ultimately inhibition of inflammation.
