A mitochondrial pyruvate dehydrogenase bypass in the yeast Saccharomyces cerevisiae.
Spheroplasts of the yeast Saccharomyces cerevisiae oxidize pyruvate at a high 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 pyruvate decarboxylase-negative mutants, the oxidation of pyruvate by permeabilized spheroplasts was abolished. In contrast, deletion of the gene (PDA1) encoding the E1alpha subunit of the pyruvate dehydrogenase did not affect the spheroplast respiratory rate on pyruvate but abolished the malate-dependent respiration of isolated mitochondria. Mutants disrupted for the mitochondrial acetaldehyde dehydrogenase gene (ALD7) did not oxidize pyruvate unless malate was added. We therefore propose the existence of a mitochondrial pyruvate dehydrogenase bypass different from the cytosolic one, where pyruvate is decarboxylated to acetaldehyde in the cytosol by pyruvate decarboxylase and then oxidized by mitochondrial acetaldehyde dehydrogenase. This pathway can compensate PDA1 gene deletion for lactate or respiratory glucose growth. However, the codisruption of PDA1 and ALD7 genes prevented the growth on lactate, indicating that each of these pathways contributes to the oxidative metabolism of pyruvate.
Boubekeur
S
S
Institut de Biochimie et Génétique Cellulaires du CNRS, Université Victor Ségalen Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux-cedex, France.
Bunoust
O
O
Camougrand
N
N
Castroviejo
M
M
Rigoulet
M
M
Guérin
B
B
D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008928:Mitochondria / Q000201:enzymology; D009154:Mutation; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure
D005656:Fungal Proteins; D011768:Pyruvate Dehydrogenase Complex; D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+)