A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification

Jovana Baković, Bess Yi Kun Yu, Daniel Silva, Sew Peak Chew, Sangeun Kim, Sun Hee Ahn, Laura Palmer, Lujain Aloum, Giacomo Stanzani, Oksana Malanchuk, Michael R. Duchen, Mervyn Singer, Valeriy Filonenko, Tae Hoon Lee, Mark Skehel, Ivan Gout

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Peroxiredoxins (Prdxs) are antioxidant enzymes that catalyse the breakdown of peroxides and regulate redox activity in the cell. Peroxiredoxin 5 (Prdx5) is a unique member of Prdxs, which displays a wider subcellular distribution and substrate specificity and exhibits a different catalytic mechanism when compared to other members of the family. Here, the role of a key metabolic integrator coenzyme A (CoA) in modulating the activity of Prdx5 was investigated. We report for the first time a novel mode of Prdx5 regulation mediated via covalent and reversible attachment of CoA (CoAlation) in cellular response to oxidative and metabolic stress. The site of CoAlation in endogenous Prdx5 was mapped by mass spectrometry to peroxidatic cysteine 48. By employing an in vitro CoAlation assay, we showed that Prdx5 peroxidase activity is inhibited by covalent interaction with CoA in a dithiothreitol-sensitive manner. Collectively, these results reveal that human Prdx5 is a substrate for CoAlation in vitro and in vivo, and provide new insight into metabolic control of redox status in mammalian cells.

Original languageBritish English
Pages (from-to)91-102
Number of pages12
JournalMolecular and Cellular Biochemistry
Issue number1-2
StatePublished - 1 Nov 2019


  • Coenzyme A (CoA)
  • Oxidative stress
  • Peroxiredoxin 5 (Prdx5)
  • Reactive oxygen species (ROS)
  • Redox regulation


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