スズキ　ノリユキ   Suzuki Noriyuki   鈴木　紀行    所属   東邦大学  薬学部 薬学科    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis.
掲載誌名	正式名：Nature structural & molecular biology ISSNコード：15459985
掲載区分	国外
著者・共著者	Hiroaki Fujita, Yu-ki Tanaka, Noriyuki Suzuki, Sota Kuno, Yasumitsu Ogra, Kazuhiro Iwai.
発行年月	2024/06/12
概要	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.