Glrx2, encoding mitochondrial glutaredoxin2 (Grx2), is an important redox regulator [1,2,3,4,5]. It is involved in maintaining the balance of thiol-dependent redox systems and participates in multiple biological processes related to oxidative stress response, such as protecting cells from oxidative damage [1,2,3,4,5]. The Nrf2-mediated pathway is one of the associated pathways [1].

In gene knockout studies, mitochondrial Glrx2 knockout in mice sensitized them to acetaminophen-induced hepatotoxicity. Glrx2 deletion hindered Nrf2-mediated compensatory recovery of thiol-dependent redox systems, leading to a more oxidized cellular state and enhanced apoptosis-inducing factor (AIF) pathway-mediated oxidative damage [1]. In contrast, in male mice, ablating the Glrx2 gene protected against non-alcoholic fatty liver disease (NAFLD) by enhancing mitochondrial redox buffering capacity [2].

In conclusion, Glrx2 plays a crucial role in maintaining cellular redox homeostasis. Gene knockout mouse models have revealed its significance in diseases like acetaminophen-induced hepatotoxicity and NAFLD, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Li, Jing, Tang, Xuewen, Wen, Xing, Du, Yatao, Lu, Jun. 2022. Mitochondrial Glrx2 Knockout Augments Acetaminophen-Induced Hepatotoxicity in Mice. In Antioxidants (Basel, Switzerland), 11, . doi:10.3390/antiox11091643. https://pubmed.ncbi.nlm.nih.gov/36139718/

2. Grayson, Cathryn, Chalifoux, Olivia, Russo, Mariana De Sa Tavares, Agellon, Luis B, Mailloux, Ryan J. 2024. Ablating the glutaredoxin-2 (Glrx2) gene protects male mice against non-alcoholic fatty liver disease (NAFLD) by limiting oxidative distress. In Free radical biology & medicine, 224, 660-677. doi:10.1016/j.freeradbiomed.2024.09.016. https://pubmed.ncbi.nlm.nih.gov/39278573/

3. Nagy, Norbert, Malik, Gautam, Tosaki, Arpad, Maulik, Nilanjana, Das, Dipak K. 2007. Overexpression of glutaredoxin-2 reduces myocardial cell death by preventing both apoptosis and necrosis. In Journal of molecular and cellular cardiology, 44, 252-60. doi:. https://pubmed.ncbi.nlm.nih.gov/18076901/

4. Diotte, Nicole M, Xiong, Ye, Gao, Jinping, Chua, Balvin H L, Ho, Ye-Shih. 2008. Attenuation of doxorubicin-induced cardiac injury by mitochondrial glutaredoxin 2. In Biochimica et biophysica acta, 1793, 427-38. doi:10.1016/j.bbamcr.2008.10.014. https://pubmed.ncbi.nlm.nih.gov/19038292/

5. Liu, Yuna, Gong, Jinlin, Wang, Qing, Zhao, Lei, Wu, Zhenan. 2023. Activation of the Nrf2/HO-1 axis by glutaredoxin 2 overexpression antagonizes vascular endothelial cell oxidative injury and inflammation under LPS exposure. In Cytotechnology, 76, 167-178. doi:10.1007/s10616-023-00606-x. https://pubmed.ncbi.nlm.nih.gov/38495299/