Liver specific disruption of Glutaredoxin 3 leads to iron accumulation and impaired cellular iron homeostasis

The role mammalian glutaredoxin 3 (Grx3) plays in iron homeostasis is poorly understood. Here we report the generation and characterization of a Grx3 liver-specific knockout (LKO) mouse strain. Grx3 LKO and WT mice had similar growth however, the LKO mice had elevated iron concentration and ROS production leading to impaired liver function and altered cytosolic and nuclear Fe-S cluster assembly. The expression of hepatic FTH1 and other iron homeostasis genes appeared to correlate with the elevation in iron concentration. Interestingly, this increase in hepatic FTH1 showed an inverse correlation with the abundance of autophagy pathway proteins. These findings suggest a crucial role for Grx3 in regulating hepatocyte iron homeostasis by controlling cellular storage protein turnover and recycling via the autophagy pathway. (c) 2023 Elsevier Inc. All rights reserved.

Automated summary

The role of mammalian glutaredoxin 3 (Grx3) in iron homeostasis is investigated using a liver-specific knockout mouse model. The knockout mice show increased iron concentration and ROS production, leading to impaired liver function and altered Fe-S cluster assembly. The expression of hepatic FTH1 and autophagy pathway proteins exhibits an inverse correlation, suggesting that Grx3 regulates hepatocyte iron homeostasis by controlling protein turnover and recycling via the autophagy pathway.