FIGURE 10.

Role of mitochondria in alcohol metabolism in the liver. The metabolism of alcohol in the liver is dependent on three major pathways: 1) the conversion of ethanol to acetaldehyde by ADH, utilizing NAD⁺ that occurs in the cytoplasm; 2) the conversion of acetaldehyde to acetate by ALDH2, utilizing NAD⁺ that occurs in the mitochondrial matrix; and 3) mitochondrial respiration, which oxidizes NADH to regenerate NAD⁺ for alcohol metabolism that occurs in the mitochondrial inner membrane. Both alcohol and acetaldehyde metabolism are rate-limited by the availability of NAD⁺. Thus, the rate-limiting step in alcohol metabolism is mitochondrial respiration to regenerate NAD⁺. Chronic alcohol feeding to mice increases mitochondrial respiration, due to increased levels of complexes I, IV, and V, thus enhancing the capacity of liver to metabolize alcohol. Increased mitochondrial respiration caused by alcohol may, however, lead to hypoxia in the liver.