Glrx2, encoding mitochondrial glutaredoxin2 (Grx2), is an important redox regulator. It participates in thiol-redox compensatory response, and is involved in multiple pathways related to oxidative stress and cell survival [1,2,3,4]. Glrx2 is crucial for maintaining the redox balance in mitochondria, which is essential for normal cellular function and resistance to various stressors [1,2,3,4].

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, ablating the Glrx2 gene protected male mice against non-alcoholic fatty liver disease (NAFLD) by enhancing mitochondrial redox buffering capacity, likely due to modulation of mitochondrial S-glutathionylation signaling [2].

In conclusion, Glrx2 plays a vital role in maintaining mitochondrial redox homeostasis. Mouse models with Glrx2 knockout have provided valuable insights into its functions in liver-related diseases, such as acetaminophen-induced hepatotoxicity and NAFLD, highlighting its potential as a therapeutic target for these conditions [1,2].