PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis.
Nat Struct Mol Biol
; 31(8): 1277-1285, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38867112
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 21st 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Selenium
/
Peroxiredoxin VI
/
Ferroptosis
/
Phospholipid Hydroperoxide Glutathione Peroxidase
/
Iron
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Struct Mol Biol
/
Nat. struct. mol. biol
/
Nature structural & molecular biology
Journal subject:
BIOLOGIA MOLECULAR
Year:
2024
Document type:
Article
Affiliation country:
Japan
Country of publication:
United States