The critical role of redox regulation of PTEN and peroxiredoxin III in alcoholic fatty liver

Hepatic steatosis and subsequent fatty liver disease are developed in response to alcohol consumption. Reactive oxygen species (ROS) are thought to play an important role in the alcoholic fatty liver disease (AFLD). However, the molecular targets of ROS and the underlying cellular mechanisms are unknown. Here, we investigate roles of peroxiredoxin III and redox regulation of phosphatase and tension homolog deleted on chromosome 10 (PTEN) in the alcoholic fatty liver. Alcohol-induced mitochondrial oxidative stress was found to contribute to reversible oxidation of PTEN, which results in Akt and MAPK hyperactivation with elevated levels of the lipogenesis regulators SREBP1c and PPAR gamma. Moreover, mitochondrial peroxiredoxin III was found to have antagonistic effects on lipogenesis via the redox regulation of PTEN by removing ROS, upon alcohol exposure. This study demonstrated that redox regulation of PTEN and peroxiredoxin III play crucial roles in the development of AFLD.

Automated summary

This study investigates the roles of peroxiredoxin III and redox regulation of phosphatase and tension homolog deleted on chromosome 10 (PTEN) in alcoholic fatty liver disease. It found that alcohol-induced mitochondrial oxidative stress contributes to reversible oxidation of PTEN, leading to hyperactivation of Akt and MAPK with elevated levels of lipogenesis regulators. Peroxiredoxin III in mitochondria was found to have antagonistic effects on lipogenesis by removing ROS, highlighting the crucial roles of redox regulation of PTEN and peroxiredoxin III in the development of AFLD.