The role of peroxiredoxin 6 in biosynthesis of FAHFAs

0565458 - FGÚ 2023 RIV US eng J - Journal Article
Palůchová, Veronika - Čajka, Tomáš - Durand, T. - Vigor, C. - Dodia, Ch. - Chatterjee, S. - Fisher, A. B. - Kuda, Ondřej
The role of peroxiredoxin 6 in biosynthesis of FAHFAs.
Free Radical Biology and Medicine. Roč. 193, Nov 20 Part 2 (2022), s. 787-794. ISSN 0891-5849. E-ISSN 1873-4596
R&D Projects: GA MŠMT(CZ) LTAUSA18104
Grant - others:AV ČR(CZ) LQ200111901
Program: Prémie Lumina quaeruntur
Institutional support: RVO:67985823
Keywords : peroxiredoxin * FAHFA * lipid oxidation * adipose tissue * linoleic acid
OECD category: Biochemistry and molecular biology
Impact factor: 7.4, year: 2022
Method of publishing: Limited access
https://doi.org/10.1016/j.freeradbiomed.2022.11.015

Peroxiredoxin 6 (Prdx6) is a multifunctional enzyme, a unique member of the peroxiredoxin family, with an important role in antioxidant defense. Moreover, it has also been linked with the biosynthesis of anti-inflammatory and anti-diabetic lipids called fatty acid esters of hydroxy fatty acids (FAHFAs) and many diseases, including cancer, inflammation, and metabolic disorders. Here, we performed metabolomic and lipidomic profiling of subcutaneous adipose tissue from mouse models with genetically modified Prdx6. Deletion of Prdx6 resulted in reduced levels of FAHFAs containing 13-hydroxylinoleic acid (13-HLA). Mutation of Prdx6 C47S impaired the glutathione peroxidase activity and reduced FAHFA levels, while D140A mutation, responsible for phospholipase A2 activity, showed only minor effects. Targeted analysis of oxidized phospholipids and triacylglycerols in adipocytes highlighted a correlation between FAHFA and hydroxy fatty acid production by Prdx6 or glutathione peroxidase 4. FAHFA regioisomer abundance was negatively affected by the Prdx6 deletion, and this effect was more pronounced in longer and more unsaturated FAHFAs. The predicted protein model of Prdx6 suggested that the monomer-dimer transition mechanism might be involved in the repair of longer-chain peroxidized phospholipids bound over two monomers and that the role of Prdx6 in FAHFA synthesis might be restricted to branching positions further from carbon 9. In conclusion, our work linked the peroxidase activity of Prdx6 with the levels of FAHFAs in adipose tissue.
Permanent Link: https://hdl.handle.net/11104/0336992