Fig. 2. Ferroptosis mechanisms and regulations.

The anti-transporter systems of SLC7A11 and SLC3A2 are primarily responsible for cystine uptake in oxidative extracellular environment. With the reductive extracellular environment, SLC7A10 mediates direct uptake of cysteine into the cytosol, leading to activation of GPX4. Moreover, intracellular cysteine levels can be replenished by conversion of methionine amino acid into cysteine through transulfurylation mechanism. The FAT/FATP system mediates uptake of arachidonic acid and adrenoyltic acid, which are key substrates for the initiation of lipid peroxidation. Finally, various compounds can target GPX4, Fe²⁺ overload and SLC7A11-SLC3A2 system thereby, manipulating ferroptotic fate of the cell.