Iron as a therapeutic target in chronic liver disease

Figure 1 Simplified pathways of ferroptosis and site of action of the main ferroptosis modulators. Ferroptosis is mediated through excess intracellular iron in the labile iron pool (LIP). Ferritinophagy is a major source of LIP, leading to the production of reactive oxygen species (ROS) by mitochondria and lipid peroxidation. Deranged function of the system Xc- causes reduction of glutathione (GSH) and glutathione peroxidase 4 (GPX4) and an increased activity of lipoxygenases (LOXs), augmenting lipid peroxidation. Ferroptosis modulators act by interfering with components of this complicated pathway. Red arrows indicate inhibition. CoQ10: Coenzyme Q10; GSSG: Glutathione disulfide; MVA: Modified vaccinia virus Ankara; PUFAs: Polyunsaturated fatty acids; SLC3A2: Solute carrier family 3 member 2; SLC7A11: Solute carrier family 7 member 11; TRF1: Transferrin receptor 1.