Ferroptotic hydroperoxy-phospholipids generated by 15LO1–PEBP1 complexes induce compensatory autophagic responses. (A) HPLC/MS analysis showing RSL3 induced 15-HpETE-PE in HAECs stimulated with IL-13. HAECs were stimulated with IL-13 for 5 d before RSL3 treatment (10 μM, overnight), with DMSO as control. (B) RSL3 enhanced IL-13–induced LC3-II expression measured by western blot. HAECs were stimulated with IL-13 for 5 d before treatment with RSL3 (10 μM, overnight), with DMSO as control. (C) siGPx4 transfection increased IL-13–induced LC3-II as measured by western blot. HAECs transfected with siGPX4 were all stimulated with IL-13 for 5 d, with scramble siRNA as the negative control. (D) Exogenous 15-HpETE-PE induced LC3-II expression as measured by western blot in HAECs. HAECs with siGPX4 transfection were cultured under ALI (without IL-13 stimulation) for 5 d before treatment with 15-HpETE-PE (10 μg/mL), with DMPE as the control. CTL, control; HPLC, high performance liquid chromatography; MS, mass spectrometry; DMPE, dimyristoyl-sn-glycero-3-phosphoethanolamine; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.