Role of MGST1 in reactive intermediate-induced injury

Microsomal glutathione transferase (MGST1, EC 2.5.1.18) is a membrane bound glutathione transferase extensively studied for its ability to detoxify reactive intermediates, including metabolic electrophile intermediates and lipophilic hydroperoxides through its glutathione dependent transferase and peroxidase activities. It is expressed in high amounts in the liver, located both in the endoplasmic reticulum and the inner and outer mitochondrial membranes. This enzyme is activated by oxidative stress. Binding of GSH and modification of cysteine 49 (the oxidative stress sensor) has been shown to increase activation and induce conformational changes in the enzyme. These changes have either been shown to enhance the protective effect ascribed to this enzyme or have been shown to contribute to cell death through mitochondrial permeability transition pore formation. The purpose of this review is to elucidate how one enzyme found in two places in the cell subjected to the same conditions of oxidative stress could both help protect against and contribute to reactive oxygen species-induced liver injury.