Figure 1.

Regulatory pathways of ferroptosis. The figure briefly shows the representative pathways of ferroptosis, which are also involved in immune response and autoimmunity. GSH-GPX4, FSP1-CoQ10, and GCH1-BH4 pathways are considered as the three major stand-alone mechanisms modulating ferroptosis. The micronutrient selenium is required for biosynthesis of GPX4. CoQ10 is another important antioxidant molecule which can be reduced to CoQ10H2 by FSP1 and hence protect the cells from ferroptosis. The GCH1-BH4 axis suppresses ferroptosis by regulating the antioxidant BH4, CoQ10, and lipid peroxidation. In addition, AMPK plays an energy stress-mediated protective role against ferroptosis. Further, the mevalonate pathway can generate anti-ferroptotic biomolecules such as CoQ10 and IPP to participate in ferroptosis regulation. FSP1, ferroptosis suppressor protein 1; GCH1; GTP cyclohydrolase-1; BH4, tetrahydrobiopterin; Se, selenium; TfR, transferrin receptor; PUFA, polyunsaturated fatty acid; PL-PUFA, phospholipid containing polyunsaturated fatty acid chain. IPP, isopentenyl-pyrophosphate.