PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis.

Autor: Fujita H; Department of Molecular and Cellular Physiology, Kyoto University School of Medicine, Kyoto, Japan. fujisan@mcp.med.kyoto-u.ac.jp., Tanaka YK; Laboratory of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan., Ogata S; Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan., Suzuki N; Laboratory of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan., Kuno S; Department of Molecular and Cellular Physiology, Kyoto University School of Medicine, Kyoto, Japan.; Department of Radiation Oncology, New York University Langone Health, New York, NY, USA., Barayeu U; Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan., Akaike T; Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan., Ogra Y; Laboratory of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan., Iwai K; Department of Molecular and Cellular Physiology, Kyoto University School of Medicine, Kyoto, Japan. kiwai@mcp.med.kyoto-u.ac.jp.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2024 Aug; Vol. 31 (8), pp. 1277-1285. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1038/s41594-024-01329-z
Abstrakt: 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 the efficiency of intracellular selenium utilization by transferring selenium between proteins within the selenocysteyl-tRNA [Ser]Sec synthesis machinery, leading to efficient synthesis of selenocysteyl-tRNA [Ser]Sec . These findings highlight previously unidentified selenium metabolic systems and provide new insights into ferroptosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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