Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell signaling

Peroxiredoxin 6 represents a widely distributed group of peroxiredoxins that contain a single conserved cysteine in the protein monomer (1-cys Prdx). The cys when oxidized to the sulfenic form is reduced with glutathione (GSH) catalyzed by the π isoform of GSH-S-transferase. Three enzymatic activities of the protein have been described:1) peroxidase with H2O2, short chain hydroperoxides, and phospholipid hydroperoxides as substrates; 2) phospholipase A2 (PLA2); and 3) lysophosphatidylcholine acyl transferase (LPCAT). These activities have important physiological roles in antioxidant defense, turnover of cellular phospholipids, and the generation of superoxide anion via initiation of the signaling cascade for activation of NADPH oxidase (type 2). The ability of Prdx6 to reduce peroxidized cell membrane phospholipids (peroxidase activity) and also to replace the oxidized sn-2 fatty acyl group through hydrolysis/reacylation (PLA2 and LPCAT activities) provides a complete system for the repair of peroxidized cell membranes. •Prdx6 expresses peroxidase, phospholipase A2, and lysophosphatidylcholine acyl transferase activities.•Reduction and resolution of oxidized Prdx6 is mediated by GSH catalyzed by GSH S-transferase π.•Prdx6 is a complete enzyme for the repair of peroxidized cell membranes.•Prdx6 participates in the synthesis and degradation of cellular phospholipids.•Prdx6 generates the lysophosphatidic acid that leads to activation of NADPH oxidase (type 2).