Biochemical basis of mitochondrial acetaldehyde dismutation in Saccharomyces cerevisiae

Abstract

The reduction of acetaldehyde to ethanol plays a key role in sugar metabolism of baker's yeast, Saccharomyces cerevisiae, by allowing regeneration of NAD+ from glycolytic NADH+H+. The in vivo significance of the reaction catalyzed by alcohol dehydrogenase (ADH) has been verified by mutants (adhl) deficient in ADH I, one of the four known ADH isozymes. Such mutant cells grow slowly on glucose, and growth is entirely dependent on mitochondrial functions (23). Despite this requirement for a functional respiratory chain in adhi mutants, glucose is largely converted to the major fermentation products, glycerol and ethanol, and to minor products such as acetaldehyde and acetate. We showed recently that the residual ethanol production in adhl mutant cells (approximately 30% of wild-type level) cannot be attributed to any of the known ADH isozymes (ADH II through ADH IV) by using mutant cells carrying null alleles at the four ADH loci (9). The existence of another cytoplasmic NAD+-dependent ADH isozyme was also ruled out since adh°cells cannot grow in a medium containing ethanol as the sole source of carbon. Rather, acetaldehyde reduction in adh/ cells occurs inside mitochondria. In fact, mitochondrial preparations from glucose-grown cells can quantitatively convert acetaldehyde to ethanol and acetate. This dismutation of acetaldehyde requires a functional respiratory chain, which is consistent with the finding that ethanol formation in adh/ cells is blocked by antimycin A.

Fusarium oxysporum Adh1 has dual fermentative and oxidative functions and is involved in fungal virulence in tomato plants

“…6A). We interpret that this could be due to the presence of an acetaldehyde dismutating activity, which has been described in the yeast S. cerevisiae (Thielen and Ciriacy, 1991) and is responsible for ethanol production at about 30% of the wild-type level in S. cerevisiae cells deficient in all four known genes coding for alcohol dehydrogenases (ADHI through ADH4) (Drewke et al, 1990). The presence of another fermentative Adh produced in aerobically grown cells of mutants AC2 and AC3 is ruled out, in part by their allyl alcohol-resistance phenotype and by the absence of Adh activity bands in the zymogram pattern of these strains.…”

Intracellular Expression of Vitreoscilla Hemoglobin Alters the Aerobic Metabolism of Saccharomyces cerevisiae

“…A more likely model can be found by the recent discovery of a novel mitochondrial acetaldehyde dismutation pathway. The production of ethanol and acetate from this pathway inside the mitochondria is dependent on electron transport (Thielen and Ciriacy, 1991). Therefore, if the effect of VHb is to influence some key steps involved in electron transport, the net result would be an alteration in ethanol production.…”

The malate–aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast

“…The mitochondiral components, Aat1 and Mdh1, convert mitochondrial malate into aspartate, with the reverse reactions occurring on the cytoplasmic side of the mitochondrial membrane. The ethanol-acetaldehyde shuttle, consisting of mitochondrial alcohol dehydrogenase (Adh3) (Young and Pilgrim 1985;Bakker et al 2000), and cytosolic alcohol dehydrogenase (Adh1/Adh2) (Thielen and Ciriacy 1991), creates a symmetrical shuttle system for the interconversion of ethanol and acetaldehyde between the mitochondrial and cytoplasmic pools. Because both ethanol and acetaldehyde diffuse freely across biological membranes, it cannot exchange NADH and NAD against a concentration gradient.…”