A mitochondrial pyruvate dehydrogenase bypass in the yeast Saccharomyces cerevisiae

Spheroplasts of the yeast Saccharomyces cerevisiae oxidize pyruvate at a hi gh respiratory rate, whereas isolated mitochondria do not unless malate is added. We show that a cytosolic factor, pyruvate decarboxylase, is required for the non-malate-dependent oxidation of pyruvate by mitochondria. In pyr uvate decarboxylase-negative mutants, the oxidation of pyruvate by permeabi lized spheroplasts was abolished. In contrast, deletion of the gene (PDA1) encoding the E1 alpha subunit of the pyruvate dehydrogenase did not affect the spheroplast respiratory rate on pyruvate but abolished the malate-depen dent respiration of isolated mitochondria. Mutants disrupted for the mitoch ondrial acetaldehyde dehydrogenase gene (ALD7) did not oxidize pyruvate unl ess malate was added. We therefore propose the existence of a mitochondrial pyruvate dehydrogenase bypass different from the cytosolic one, where pyru vate is decarboxylated to acetaldehyde in the cytosol by pyruvate decarboxy lase and then oxidized by mitochondrial acetaldehyde dehydrogenase. This pa thway can compensate PDA1 gene deletion for lactate or respiratory glucose growth. However, the codisruption of PDA1 and ALD7 genes prevented the grow th on lactate, indicating that each of these pathways contributes to the ox idative metabolism of pyruvate.