Involvement of Candida albicans pyruvate dehydrogenase complex protein X (Pdx1) in filamentation

Abstract

For 50 years, physiologic studies in Candida albicans have associated fermentation with filamentation and respiration with yeast morphology. Analysis of the mitochondrial proteome of a C. albicans NDH51 mutant, known to be defective in filamentation, identified increased expression of several proteins in the respiratory pathway. Most notable was a 15-fold increase in pyruvate dehydrogenase complex protein X (Pdx1), an essential component of the pyruvate dehydrogenase complex. In basal salts medium with < or = 100 mM glucose as carbon source, two independent pdx1 mutants displayed a filamentation defect identical to ndh51; reintegration of one PDX1 allele restored filamentation. Concentrations of glucose < or = 100 mM did not correct the filamentation defect. Expanding on previous work, these studies suggest that increased expression of proteins extraneous to the electron transport chain compensates for defects in the respiratory pathway to maintain yeast morphology. Mitochondrial proteomics can aid in the identification of C. albicans genes not previously implicated in filamentation.

Goa1p of Candida albicans Localizes to the Mitochondria during Stress and Is Required for Mitochondrial Function and Virulence

“…This observation demonstrates the importance of respiratory metabolism in filamentation of C. albicans. Interestingly, there remains a controversy over the role of metabolic status associated with morphogenesis since both a need for and a lack of an intact respiratory pathway have been both suggested as important (10,36,37,42,54). Our data support the former conclusion.…”

“…There was no difference in growth among strains on YPD agar containing tert-butyl hydrogen peroxide and potassium superoxide (data not shown). Thus, GOA1 is required for protection to some but not all types of oxidants, a result we have observed with the C. albicans ssk2⌬ null mutant (54). We also evaluated the killing of each strain ( (Fig.…”

Simvastatin Inhibits Candida albicans Biofilm In Vitro

“…Candida albicans laboratory strain BWP17wt and the isogenic mutants deleted for both alleles of NDH51 (ndh51) and PDX1 (pdx1-29) have been previously described (23,24), as have clinical isolates from blood, skin, and mucosal surfaces (35). All strains were maintained at Ϫ80°C in 20% glycerol.…”

“…Recently, our laboratory characterized two mitochondrial mutants in which the generation of acetyl CoA is impaired (23,24). Deletion of both copies of the gene encoding either complex I of the electron transport chain (NDH51) or pyruvate dehydrogenase complex protein X (PDX1) blocks the generation of acetyl CoA.…”

“…Deletion of both copies of the gene encoding either complex I of the electron transport chain (NDH51) or pyruvate dehydrogenase complex protein X (PDX1) blocks the generation of acetyl CoA. Although we originally reported that these mutants displayed a wild-type phenotype with regard to growth, replication or hyphal formation in rich medium (23,24), we subsequently found that biofilm formation, as indicated by safranin staining of exopolysaccharide matrix, was significantly impaired in both mutants ( Fig. 1) (25)(26)(27).…”