Peroxiredoxin 6: a bifunctional enzyme with glutathione peroxidase and phospholipase A₂ activities

Antioxid Redox Signal. 2011 Aug 1;15(3):831-44. doi: 10.1089/ars.2010.3412. Epub 2011 Mar 31.


Peroxiredoxin 6 (Prdx6) is the prototype and the only mammalian 1-Cys member of the Prdx family. Major differences from 2-Cys Prdxs include the use of glutathione (GSH) instead of thioredoxin as the physiological reductant, heterodimerization with πGSH S-transferase as part of the catalytic cycle, and the ability either to reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or to hydrolyze the sn-2 ester (alkyl) bond of phospholipids (phospholipase A(2) [PLA(2)] activity). The bifunctional protein has separate active sites for peroxidase (C47, R132, H39) and PLA(2) (S32, D140, H26) activities. These activities are dependent on binding of the protein to phospholipids at acidic pH and to oxidized phospholipids at cytosolic pH. Prdx6 can be phosphorylated by MAP kinases at T177, which markedly increases its PLA(2) activity and broadens its pH-activity spectrum. Prdx6 is primarily cytosolic but also is targeted to acidic organelles (lysosomes, lamellar bodies) by a specific targeting sequence (amino acids 31-40). Oxidant stress and keratinocyte growth factor are potent regulators of Prdx6 gene expression. Prdx6 has important roles in both antioxidant defense based on its ability to reduce peroxidized membrane phospholipids and in phospholipid homeostasis based on its ability to generate lysophospholipid substrate for the remodeling pathway of phospholipid synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antioxidants / metabolism
  • Catalytic Domain
  • Fibroblast Growth Factor 7 / genetics
  • Fibroblast Growth Factor 7 / metabolism
  • Gene Expression Regulation
  • Glutathione Peroxidase / chemistry*
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Glutathione Transferase / chemistry
  • Humans
  • Molecular Sequence Data
  • Oxidative Stress / physiology
  • Peroxiredoxin VI / chemistry*
  • Peroxiredoxin VI / genetics
  • Peroxiredoxin VI / metabolism
  • Phospholipases A2 / chemistry*
  • Phospholipases A2 / genetics
  • Phospholipases A2 / metabolism
  • Phospholipids / biosynthesis
  • Protein Structure, Tertiary


  • Antioxidants
  • Phospholipids
  • Fibroblast Growth Factor 7
  • Peroxiredoxin VI
  • Glutathione Peroxidase
  • Glutathione Transferase
  • Phospholipases A2