PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis.

ABSTRACT: Ferroptosis is a form of regulated cell death induced by iron-dependent accumulation of lipid hydroperoxides. Selenoprotein glutathione peroxidase 4 (GPX4) suppresses ferroptosis by detoxifying lipid hydroperoxides via a catalytic selenocysteine (Sec) residue. Sec, the genetically encoded 21^st amino acid, is biosynthesized from a reactive selenium donor on its cognate tRNA^[Ser]Sec. It is thought that intracellular selenium must be delivered 'safely' and 'efficiently' by a carrier protein owing to its high reactivity and very low concentrations. Here, we identified peroxiredoxin 6 (PRDX6) as a novel selenoprotein synthesis factor. Loss of PRDX6 decreases the expression of selenoproteins and induces ferroptosis via a reduction in GPX4. Mechanistically, PRDX6 increases t

SUBMITTER: Fujita H 

PROVIDER: S-EPMC11327102 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature