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Cellular iron uptake (via transferrin receptor TFRC), storage (in ferritin), and release (via ferritinophagy mediated by NCOA4) are tightly regulated ( 2.1.2 Transcriptional control by Nrf2 Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master transcriptional regulator of the antioxidant response and a central mediator of cellular defenses against ferroptosis ( Nrf2 activation upregulates key ferroptosis defense components ( - subunits (SLC7A11 and SLC3A2), promoting cystine uptake and GSH biosynthesis ( However, in the context of chronic diseases like asthma, sustained or dysregulated Nrf2 activation can exhibit paradoxical, pro-ferroptotic effects ( 2.2 Regulation of iron metabolism: IRP2, ferritinophagy, and systemic influences Iron availability, particularly labile Fe 2+ , is indispensable for lipid peroxidation and the execution of ferroptosis ( Key regulatory targets include: Transferrin Receptor 1 (TfR1), whose mRNA is stabilized upon IRP2 binding to 3′ UTR IREs to enhance iron uptake

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