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Figure 1. UV-induced ferroptosis in skin cells and its link to photoaging. Ultraviolet irradiation increases ROS and p53 activity, which suppresses SLC7A11/SLC3A2 (system Xc^-) and limits cystine import for GSH synthesis (via GCL/GSS), thereby weakening GPX4-mediated reduction of PUFA-OOH. Meanwhile, iron is imported through Tf/TfR1, reduced by STEAP3, transported by DMT1, mobilized via NCOA4-mediated ferritinophagy, and exported by FPN1/SLC40A1; increased LIP drives Fenton chemistry. Lipid peroxidation is promoted by membrane PUFA-PL remodeling (ACSL4 → LPCAT3) and lipoxygenases (e.g., ALOX15), culminating in ferroptosis. Parallel antioxidant systems such as FSP1-CoQ10 (and mitochondrial DHODH) counteract phospholipid peroxidation independently of GPX4. The downstream consequences in skin include MMP-1/-3/-9 up-regulation, collagen degradation, and loss of elasticity, contributing to photoaging. Created with BioRender.com. ROS: Reactive oxygen species; SLC7A11: solute carrier family 7 member 11; SLC3A2: solute carrier family 3 member 2; GSH: glutathione; GCL: glutamate-cysteine ligase; GSS: glutathione synthetase; GPX4: glutathione peroxidase 4; PUFA-OOH: polyunsaturated fatty acid hydroperoxide; Tf: transferrin; TfR1: transferrin receptor 1; STEAP3: six-transmembrane epithelial antigen of prostate 3; DMT1: divalent metal transporter 1; NCOA4: nuclear receptor coactivator 4; FPN1: ferroportin 1; SLC40A1: solute carrier family 40 member 1; LIP: labile iron pool; PUFA-PL: polyunsaturated fatty acid-phospholipid; ACSL4: acyl-CoA synthetase long-chain family member 4; LPCAT3: lysophosphatidylcholine acyltransferase 3; ALOX15: arachidonate 15-lipoxygenase; FSP1: ferroptosis suppressor protein 1; CoQ10: coenzyme Q10; DHODH: dihydroorotate dehydrogenase; MMP: matrix metalloproteinase.