Involvement of Candida albicans NADH dehydrogenase complex I in filamentation

McDonough, Justin A.; Bhattacherjee, Vasker; Sadlon, Tania; Hostetter, Margaret K.

doi:10.1016/s1087-1845(02)00007-5

Cited by 53 publications

(57 citation statements)

References 36 publications

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“…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.…”

Section: Discussionsupporting

confidence: 80%

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

et al. 2009

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Using a Tn7 transposon library of Candida albicans, we have identified a mutant that exhibited sensitivity in drop plate assays to oxidants such as menadione and hydrogen peroxide. To verify the role of the mutated gene in stress adaptation, null mutants were constructed and phenotypically characterized. Because of its apparent functions in growth and oxidant adaptation, we have named the gene GOA1. Goa1p appears to be unique to the CTG subclade of the Saccharomycotina, including C. albicans. Mutants of C. albicans lacking goa1 (strain GOA31) were more sensitive to 6 mM H 2 O 2 and 0.125 mM menadione than the wild type (wt) or a genereconstituted (GOA32) strain. The sensitivity to oxidants correlated with reduced survival of the GOA31 mutant in human neutrophils and avirulence compared to control strains. Other phenotypes of GOA31 include reduced growth and filamentation in 10% serum, Spider, and SLAD agar media and an inability to form chlamydospores. Since Goa1p has an N-terminal mitochondrion localization site, we also show that green fluorescent protein-tagged Goa1p shows a mitochondrionlike distribution during oxidant or osmotic stress. Further, the inability of GOA31 to grow in medium containing lactate, ethanol, or glycerol as the sole carbon source indicates that the mitochondria are defective in the mutant. To determine how Goa1p contributes to mitochondrial function, we compared the wt, GOA32, and GOA31 strains for mitochondrial electrical membrane potential, respiration, and oxidative phosphorylation. We now show that GOA31, but not the wt or GOA32, had decreased respiration and mitochondrial membrane potential such that mutant cells are unable to drive oxidative phosphorylation. This is the first report in C. albicans of a respiratory defect caused by a loss of mitochondrial membrane potential.

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Section: Discussionsupporting

confidence: 80%

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

et al. 2009

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“…One other CI subunit protein that we have included for functional comparisons in our studies is Ndh51p, which is broadly conserved among species including fungi and mammals. 18,32 To determine their cellular functions, direct or indirect, we constructed knock-out strains of Nuo1, Nuo2, and Goa1. Common phenotypes included reduced mitochondrial respiration, ATP synthesis, and CI disassembly.…”

Section: Complex I Subunit Proteins As Drug Targetsmentioning

confidence: 99%

Exploiting mitochondria as targets for the development of new antifungals

Calderone

2016

Virulence

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“…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.…”

Section: Chemicalsmentioning

confidence: 99%

“…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.…”

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confidence: 99%

“…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).…”

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confidence: 99%

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Simvastatin Inhibits Candida albicans Biofilm In Vitro

et al. 2009

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By inhibiting the conversion of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) to mevalonate, statins impair cholesterol metabolism in humans. We reasoned that statins might similarly interfere with the biosynthesis of ergosterol, the major sterol of the yeast cell membrane. As assessed by spectrophotometric and microscopic analysis, significant inhibition of biofilm production was noted after 16-h incubation with 1, 2.5, and 5 M simvastatin, concentrations that did not affect growth, adhesion, or hyphal formation by C. albicans in vitro. Higher concentrations (10, 20, and 25 M simvastatin) inhibited biofilm by Ͼ90% but also impaired growth. Addition of exogenous ergosterol (90 M) overcame the effects of 1 and 2.5 M simvastatin, suggesting that at least one mechanism of inhibition is interference with ergosterol biosynthesis. Clinical isolates from blood, skin, and mucosal surfaces produced biofilms; biofilms from bloodstream isolates were similarly inhibited by simvastatin. In the absence of fungicidal activity, simvastatin's interruption of a critical step in an essential metabolic pathway, highly conserved from yeast to man, has unexpected effects on biofilm production by a eukaryotic pathogen. (Pediatr Res 66: 600-604, 2009)

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Involvement of Candida albicans NADH dehydrogenase complex I in filamentation

Cited by 53 publications

References 36 publications

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

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

Exploiting mitochondria as targets for the development of new antifungals

Simvastatin Inhibits Candida albicans Biofilm In Vitro

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