Prdx3, peroxiredoxin 3, is a master regulator of mitochondrial oxidative stress, acting as an efficient hydrogen peroxide (H2O2) scavenger protecting cells from mitochondrial oxidative damage and apoptosis [2,3]. It is involved in multiple pathways such as mitochondrial reactive oxygen species (ROS)/TGF-β1/Smad2/3, and its dysregulation is associated with various diseases [2]. Genetic models like KO/CKO mouse models can provide insights into its function in vivo.

In mouse models of alcoholic and non-alcoholic fatty liver diseases, hyperoxidized Prdx3 was identified as a marker for ferroptosis, suggesting ferroptosis is responsible for hepatocyte death [1]. In liver fibrosis, AAV9-Prdx3 knockdown exacerbated hepatic fibrogenesis and HSC activation, while HSC-specific Prdx3 overexpression attenuated liver fibrosis, indicating Prdx3's role in regulating this process through the mitochondrial ROS/TGF-β1/Smad2/3 pathway [2]. In intestinal I/R injury mouse models, Prdx3 expression was decreased, and its overexpression attenuated H/R-induced mitochondrial oxidative damage and apoptosis. SIRT3-mediated deacetylation of Prdx3 was shown to be crucial in alleviating this injury [3].

In conclusion, Prdx3 plays essential roles in maintaining mitochondrial oxidative balance. Model-based research, especially KO/CKO mouse models, has revealed its significance in diseases like chronic liver diseases, liver fibrosis, and intestinal I/R injury, offering potential therapeutic targets for these conditions.

References:

1. Cui, Shaojie, Ghai, Anchal, Deng, Yaqin, Achilefu, Samuel, Ye, Jin. 2023. Identification of hyperoxidized PRDX3 as a ferroptosis marker reveals ferroptotic damage in chronic liver diseases. In Molecular cell, 83, 3931-3939.e5. doi:10.1016/j.molcel.2023.09.025. https://pubmed.ncbi.nlm.nih.gov/37863053/

2. Sun, Ruimin, Tian, Xinyao, Li, Yang, Zheng, Shusen, Yao, Jihong. 2022. The m6A reader YTHDF3-mediated PRDX3 translation alleviates liver fibrosis. In Redox biology, 54, 102378. doi:10.1016/j.redox.2022.102378. https://pubmed.ncbi.nlm.nih.gov/35779442/

3. Wang, Zhanyu, Sun, Ruimin, Wang, Guangzhi, Yao, Jihong, Tian, Xiaofeng. 2019. SIRT3-mediated deacetylation of PRDX3 alleviates mitochondrial oxidative damage and apoptosis induced by intestinal ischemia/reperfusion injury. In Redox biology, 28, 101343. doi:10.1016/j.redox.2019.101343. https://pubmed.ncbi.nlm.nih.gov/31655428/