The Crucial Role of Alcohol Dehydrogenase Adh3 in Kluyveromyces marxianus Mitochondrial Metabolism

The function of mitochondrial Adh3 in the thermo-tolerant yeast Kluyveromyces marxianus was investigated. An ADH3-disrupted mutant exhibited growth retardation on non-fermentable carbon sources, except for ethanol, and this was suppressed by supplementation with antioxidants. Detailed analysis of the phenotype revealed that the mutant showed an increase in the activity of NADH dehydrogenase, sensitivity to H2O2, and accumulation of reactive oxygen species (ROS), and that these carbon sources increased the activity of succinate dehydrogenase. The increase in both activities may reflect enhanced expression of both dehydrogenases by elevation of their substrate levels. The ROS level became low when antioxidants were added. These findings suggest that the ADH3 mutation and such carbon sources cause an elevation of the substrate level of the respiratory chain and eventually of the ROS level via increased expression of primary dehydrogenases, which in turn causes cell growth retardation. Adh3 might thus play a crucial role in the control of the NADH/NAD(+) balance in mitochondria.