Differential Effect of Respiratory Inhibitors on Ergosterol Synthesis by<i>Saccharomyces cerevisiae</i>During Adaptation to Oxygen

Adams, Bruce G.; Parks, Leo W.

doi:10.1128/jb.100.1.370-376.1969

Cited by 17 publications

(5 citation statements)

References 24 publications

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“…Connections between mitochondrial dysfunction, respiratory activity and efflux levels have been reported to affect azole resistance in both C. glabrata and C. albicans. [34][35][36] Moreover, mitochondrial respiration is required to produce heme and to maintain the activity of many of the enzymes in the ergosterol biosynthesis pathway, 37,38 yet most enzymes in the ergosterol biosynthesis pathway localize primarily to the endoplasmic reticulum. 39,40 Whether they also localize to mitochondria is not known.…”

Section: Real-time Live-cell Fluorescent Imagingmentioning

confidence: 99%

Real-Time Imaging of the Azole Class of Antifungal Drugs in Live Candida Cells

et al. 2017

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Azoles are the most commonly used class of antifungal drugs, yet where they localize within fungal cells and how they are imported remain poorly understood. Azole antifungals target lanosterol 14α-demethylase, a cytochrome P450, encoded by ERG11 in Candida albicans, the most prevalent fungal pathogen. We report the synthesis of fluorescent probes that permit visualization of antifungal azoles within live cells. Probe 1 is a dansyl dye-conjugated azole, and probe 2 is a Cy5-conjugated azole. Docking computations indicated that each of the probes can occupy the active site of the target cytochrome P450. Like the azole drug fluconazole, probe 1 is not effective against a mutant that lacks the target cytochrome P450. In contrast, the azole drug ketoconazole and probe 2 retained some antifungal activity against mutants lacking the target cytochrome P450, implying that both act against more than one target. Both fluorescent azole probes colocalized with the mitochondria, as determined by fluorescence microscopy with MitoTracker dye. Thus, these fluorescent probes are useful molecular tools that can lead to detailed information about the activity and localization of the important azole class of antifungal drugs.

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Section: Real-time Live-cell Fluorescent Imagingmentioning

confidence: 99%

Real-Time Imaging of the Azole Class of Antifungal Drugs in Live Candida Cells

et al. 2017

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“…The utilization of oxygen involves pathways other than the mitochondrial transport chain and fatty acid desaturation. The stoichiometric relationship between these two mechanisms reported in this study suggests that they represent one of the main pathways of oxygen utilization; however, synthesis of ergosterol requires 9 moles of O 2 whereas desaturation of fatty acid requires only 1 mole ( Espenshade & Hughes, 2007 ; Bloch, 1969 ) and inhibition of mitochondrial activity also affected sterol synthesis ( Adams & Parks, 1969 ). Moreover, several steps of the synthesis of heme inside the mitochondria also requires oxygen.…”

Section: Discussionmentioning

confidence: 77%

Residual mitochondrial transmembrane potential decreases unsaturated fatty acid level in sake yeast during alcoholic fermentation

Sawada

Kitagaki

2016

PeerJ

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Oxygen, a key nutrient in alcoholic fermentation, is rapidly depleted during this process. Several pathways of oxygen utilization have been reported in the yeast Saccharomyces cerevisiae during alcoholic fermentation, namely synthesis of unsaturated fatty acid, sterols and heme, and the mitochondrial electron transport chain. However, the interaction between these pathways has not been investigated. In this study, we showed that the major proportion of unsaturated fatty acids of ester-linked lipids in sake fermentation mash is derived from the sake yeast rather than from rice or koji (rice fermented with Aspergillus). Additionally, during alcoholic fermentation, inhibition of the residual mitochondrial activity of sake yeast increases the levels of unsaturated fatty acids of ester-linked lipids. These findings indicate that the residual activity of the mitochondrial electron transport chain reduces molecular oxygen levels and decreases the synthesis of unsaturated fatty acids, thereby increasing the synthesis of estery flavors by sake yeast. This is the first report of a novel link between residual mitochondrial transmembrane potential and the synthesis of unsaturated fatty acids by the brewery yeast during alcoholic fermentation.

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“…Several investigators have previously shown indirect relationships between ergosterol biosynthesis and respiratory growth (1,13). The differences in sensitivity to the azasterol shown by cells cultured on either 2% ethanol or 2% glucose add to these reports.…”

Section: Discussionmentioning

confidence: 85%

Homoazasterol-mediated inhibition of yeast sterol biosynthesis

Bailey¹,

Hays²,

Parks³

1976

J Bacteriol

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A naturally occurring azasterol has been shown to inhibit sterol transmethylation in both in vitro and in vivo in the yeast Saccharomyces cerevisiae. The inhibition was competitive, with a calculated dissociation constant of 43 muM. The compound prevented the accumulation of ergosterol in aerobically adapting cells. Cultures forced to gain energy by respiration were found to be much more sensitive to growth inhibition by the azasterol than those cells fermenting glucose. The growth inhibition is reversible at low concentrations of the azasterol.

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Differential Effect of Respiratory Inhibitors on Ergosterol Synthesis bySaccharomyces cerevisiaeDuring Adaptation to Oxygen

Cited by 17 publications

References 24 publications

Real-Time Imaging of the Azole Class of Antifungal Drugs in Live Candida Cells

Real-Time Imaging of the Azole Class of Antifungal Drugs in Live Candida Cells

Residual mitochondrial transmembrane potential decreases unsaturated fatty acid level in sake yeast during alcoholic fermentation

Homoazasterol-mediated inhibition of yeast sterol biosynthesis

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