Prdx4, a member of the Prdx family, is a unique endoplasmic reticulum (ER)-resident 2-Cys antioxidant. It plays a vital role in fine-tuning hydrogen peroxide catabolism, which impacts redox balance, oxidative protein folding, and hydrogen peroxide signaling [1,3]. By coupling hydrogen peroxide (H₂O₂) catabolism with oxidative protein folding, it protects nascent proteins from alternative oxidative fates and cells from misfolded proteins, thus maintaining ER redox homeostasis [3].

In mouse models, Prdx4 deficiency has diverse effects. Prdx4-knockout (Prdx4-/y) adult and aged mice show mortality, and delayed wound healing due to increased oxidative stress, inflammation, and fewer fibroblasts [2]. Prdx4-/-mice have accelerated D-gal-induced ovarian ageing, with lower ovarian weight, disrupted HPO axis, increased atretic follicles, apoptotic granulosa cells, and elevated oxidative damage-related factors [5]. Mice lacking Prdx4 also have increased susceptibility to LPS-induced septic shock, as Prdx4 limits caspase-1 activation and inflammasome-mediated signaling [4].

In conclusion, Prdx4 is essential for maintaining redox balance, especially in the ER, and is crucial for normal physiological processes such as wound healing and ovarian function. Prdx4 KO mouse models have revealed its significance in these processes and in conditions like sepsis and ovarian ageing, highlighting its potential as a therapeutic target for related diseases.

References:

1. Jia, Wenqiao, Chen, Pengxiang, Cheng, Yufeng. . PRDX4 and Its Roles in Various Cancers. In Technology in cancer research & treatment, 18, 1533033819864313. doi:10.1177/1533033819864313. https://pubmed.ncbi.nlm.nih.gov/31311441/

2. Yamaguchi, Reimon, Guo, Xin, Zheng, Jianbo, Mochizuki, Takashi, Yamada, Sohsuke. 2021. PRDX4 Improved Aging-Related Delayed Wound Healing in Mice. In The Journal of investigative dermatology, 141, 2720-2729. doi:10.1016/j.jid.2021.04.015. https://pubmed.ncbi.nlm.nih.gov/34029576/

3. Zito, Ester. 2012. PRDX4, an endoplasmic reticulum-localized peroxiredoxin at the crossroads between enzymatic oxidative protein folding and nonenzymatic protein oxidation. In Antioxidants & redox signaling, 18, 1666-74. doi:10.1089/ars.2012.4966. https://pubmed.ncbi.nlm.nih.gov/23025503/

4. Lipinski, Simone, Pfeuffer, Steffen, Arnold, Philipp, Tholey, Andreas, Rosenstiel, Philip. 2019. Prdx4 limits caspase-1 activation and restricts inflammasome-mediated signaling by extracellular vesicles. In The EMBO journal, 38, e101266. doi:10.15252/embj.2018101266. https://pubmed.ncbi.nlm.nih.gov/31544965/

5. Liang, Xiuru, Yan, Zhengjie, Ma, Weiwei, Liu, Jiayin, Meng, Yan. 2020. Peroxiredoxin 4 protects against ovarian ageing by ameliorating D-galactose-induced oxidative damage in mice. In Cell death & disease, 11, 1053. doi:10.1038/s41419-020-03253-8. https://pubmed.ncbi.nlm.nih.gov/33311472/