NCOA4-Mediated Ferritinophagy Induces Ferroptosis and Enriches Ferritin-Containing EVs via Ferritin Phase Separation to Promote Mechanical Ventilation-Induced Pulmonary Fibrosis

MV induces ANG II/AGTR1-mediated ferritinophagy and ferroptosis in AECs. NCOA4-driven ferritin phase separation promotes ferritinophagy under mechanical stress. Ferritin-containing EVs from damaged AECs activate fibroblasts, exacerbating MVPF. Our findings underscore the pivotal role of iron metabolism dysregulation in biomechanically induced programmed cell death and intercellular communication, and reveal potential therapeutic targets for the prevention and treatment of MVPF.