Endogenous Mitochondrial Aldehyde Dehydrogenase-2 as an Antioxidant in Liver

Abstract Oxidative stress and aldehydes play an important role in the development and progression of liver diseases. Aldehyde dehydrogenase-2 (ALDH2) is one of the ALDH superfamily enzymes, which presents in mitochondria and is mainly involved in the metabolism of acetaldehyde. The antioxidation activity of ALDH2 is due to its effect of toxic aldehydes clearance. Activation of ALDH2 can exert cardioprotective effect, whereas inhibition of ALDH2 plays a role in alcohol metabolism. Many drugs including alda-1 and disulfiram can affect the activity of ALDH2. ALDH2 activity can be inhibited by oxidative stress products including 4-hydroxy-2-nonenal (4-HNE) through posttranslational modifications (PTMs). ALDH2 has genetic polymorphisms, in which the mutant ALDH2*2 proteins lead to decreased ethanol metabolic activity. It is still controversial whether the ALDH2 gene polymorphisms are closely related to alcoholic liver diseases.