The effects and mechanisms of PRDX6 on alleviating epithelial ferroptosis in COPD through enhancing the stability of ferritin and inhibiting its ferritinophagy

Ferritinophagy is a biological process in which ferritin is degraded and iron ions are released. Ferroptosis, which is characterized by phospholipid peroxidation and iron overload, is an important mechanism for cell damage repair. <fig><object-id>erj;64/suppl_68/PA4399/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>We demonstrated that iron was accumulated and peroxiredoxin (PRDX) 6, which specifically reduces phospholipid hydroperoxides, was decreased in the lungs of COPD patients. In vitro and vivo studies of smoking-induced COPD showed that Prdx6 cKO mice had more severe COPD and ferroptosis. In Beas-2B cells, deletion of PRDX6 induced ferritinophagy and the rescue of PRDX6 restored the levels of ferritin. <fig><object-id>erj;64/suppl_68/PA4399/F2</object-id><object-id>F2</object-id><object-id>F2</object-id><graphic></graphic></fig> Taken together, PRDX6 may regulate the metabolism of ferritin in COPD. The decrease and conformational change of PRDX6 may result in the dissociation of PRDX6-ferritin complex, which promotes ferritinophagy and then aggravates ferroptosis. The aim of this study is to provide new ideas and target for the treatment of COPD.