Prdx3, peroxiredoxin 3, is a master regulator of mitochondrial oxidative stress. It functions as an efficient hydrogen peroxide (H₂O₂) scavenger, protecting cells from mitochondrial oxidative damage and apoptosis. It is involved in multiple biological pathways, such as those related to oxidative stress response, ferroptosis, and cell survival [1,2].

In animal models, Prdx3 has been shown to play significant roles in various diseases. In liver fibrosis, its expression is negatively correlated with the condition. PRDX3 knockdown in mice exacerbated hepatic fibrogenesis and hepatic stellate cell (HSC) activation, while HSC-specific PRDX3 overexpression attenuated liver fibrosis, with the mechanism involving the mitochondrial reactive oxygen species (ROS)/TGF-β1/Smad2/3 pathway [1].

In intestinal ischemia/reperfusion (I/R) injury, PRDX3 expression was decreased. Overexpression of PRDX3 in Caco-2 cells significantly attenuated hypoxia/reoxygenation (H/R)-induced mitochondrial oxidative damage and apoptosis. SIRT3-mediated deacetylation of PRDX3 was found to alleviate I/R-induced mitochondrial oxidative damage and apoptosis [2].

In pulmonary fibrosis, YAP1 promoted Prdx3 expression, and forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in bleomycin-treated MLE-12 cells, while Prdx3 depletion abrogated the protective effect of YAP1 [3].

In gastric cancer, PRDX3 was overexpressed in cancer tissue compared to adjacent non-cancer tissue. Silencing PRDX3 reduced the half-inhibitory concentration (IC50) of cisplatin in AGS and MKN-74 cell lines, increased apoptosis, and upregulated the expression of cleaved caspase-3 and Bax, indicating that PRDX3 increases cisplatin resistance in gastric cancer cells [4].

In uveal melanoma, high immunohistochemical expression of PRDX3 in primary tissue was associated with metastasis and poor survival [5]. In gastric cancer, the FOXM1-ASF1B-PRDX3 axis was identified, and ASF1B regulated PRDX3 transcription in a FOXM1-dependent manner, with PRDX3 playing a role in cell proliferation and oxidative stress balance [6].

In conclusion, Prdx3 is crucial for maintaining mitochondrial function and cell survival by scavenging H₂O₂. Studies using gene-knockout or conditional-knockout mouse models have revealed its significance in diseases like liver fibrosis, intestinal I/R injury, pulmonary fibrosis, gastric cancer, and uveal melanoma. These findings provide potential therapeutic targets for treating these diseases by targeting Prdx3 and its related pathways.