Anaerobiosis induces complex changes in sterol esterification pattern in the yeast Saccharomyces cerevisiae

Valachovič, Martin

doi:10.1016/s0378-1097(01)00082-9

Cited by 23 publications

(36 citation statements)

References 11 publications

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“…The most fundamental question is why yeast contains two sterol esterification genes and yet neither is essential for survival. Previous work using are1 and are2 strains indicate that the role of Are1p is to esterify sterol intermediates, principally lanosterol, the first sterol in the pathway, whereas Are2p principally esterifies the end product ergosterol (38,48,53). Our results are similar in that we overexpressed ARE1-and ARE2-containing plasmids in an are1 are2 double deletion strain.…”

Section: Discussionsupporting

confidence: 81%

“…This could reflect differences in subcellular localizations, responses to the environment, or substrate specificity. In yeast, the Are proteins are both localized to the endoplasmic reticulum but exhibit marked substrate preferences (48,53). In this study, we confirm that, in terms of contribution to the sterol ester mass in yeast, the ARE1 gene product primarily esterifies intermediates in the sterol biosynthetic pathway such as lanosterol, whereas ARE2 is responsible for esterification of the end product ergosterol.…”

supporting

confidence: 74%

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Transcriptional Regulation of the Two Sterol Esterification Genes in the Yeast Saccharomyces cerevisiae

Jensen-Pergakes

Guo²,

Giattina³

et al. 2001

J Bacteriol

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Saccharomyces cerevisiae transcribes two genes, ARE1 and ARE2, that contribute disproportionately to the esterification of sterols. Are2p is the major enzyme isoform in a wild-type cell growing aerobically. This likely results from a combination of differential transcription initiation and transcript stability. By using ARE1 and ARE2 promoter fusions to lacZ reporters, we demonstrated that transcriptional initiation from the ARE1 promoter is significantly reduced compared to that from the ARE2 promoter. Furthermore, the half-life of the ARE2 mRNA is approximately 12 times as long as that of the ARE1 transcript. We present evidence that the primary role of the minor sterol esterification isoform encoded by ARE1 is to esterify sterol intermediates, whereas the role of the ARE2 enzyme is to esterify ergosterol, the end product of the pathway. Accordingly, the ARE1 promoter is upregulated in strains that accumulate ergosterol precursors. Furthermore, ARE1 and ARE2 are oppositely regulated by heme. Under heme-deficient growth conditions, ARE1 was upregulated fivefold while ARE2 was down-regulated. ARE2 requires the HAP1 transcription factor for optimal expression, and both ARE genes are derepressed in a rox1 (repressor of oxygen) mutant genetic background. We further report that the ARE genes are not subject to end product inhibition; neither ARE1 nor ARE2 transcription is altered in an are mutant background, nor does overexpression of either ARE gene alter the response of the ARE-lacZ reporter constructs. Our observations are consistent with an important physiological role for Are1p during anaerobic growth when heme is limiting and sterol precursors may accumulate. Conversely, Are2p is optimally required during aerobiosis when ergosterol is plentiful.

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Section: Discussionsupporting

confidence: 81%

supporting

confidence: 74%

Transcriptional Regulation of the Two Sterol Esterification Genes in the Yeast Saccharomyces cerevisiae

Jensen-Pergakes

Guo²,

Giattina³

et al. 2001

J Bacteriol

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“…However, the import characteristics of the unmodified ergosterol, in terms of the amounts associated with each fungal species, are consistent with the cholesterol levels. Exogenous ergosterol, in comparison to cholesterol, is known to be poorly esterified in S. cerevisiae (18,26). This appears to be true for all three fungal species.…”

Section: Resultsmentioning

confidence: 99%

“…The ScUpc2-regulated cell wall protein ScDan1 is involved in sterol uptake associated with the cell wall (17,24). After sterol saturation of membranes, excess imported cholesterol is esterified via ScAre1p and ScAre2p (25), while excess ergosterol remains unesterified (15,18,26). Many other genes involved in sterol uptake have been described, including several related to mitochondrial metabolism (23).…”

mentioning

confidence: 99%

Comparison of Sterol Import under Aerobic and Anaerobic Conditions in Three Fungal Species, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae

2013

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bSterol import has been characterized under various conditions in three distinct fungal species, the model organism Saccharomyces cerevisiae and two human fungal pathogens Candida glabrata and Candida albicans, employing cholesterol, the sterol of higher eukaryotes, as well as its fungal equivalent, ergosterol. Import was confirmed by the detection of esterified cholesterol within the cells. Comparing the three fungal species, we observe sterol import under three different conditions. First, as previously well characterized, we observe sterol import under low oxygen levels in S. cerevisiae and C. glabrata, which is dependent on the transcription factor Upc2 and/or its orthologs or paralogs. Second, we observe sterol import under aerobic conditions exclusively in the two pathogenic fungi C. glabrata and C. albicans. Uptake emerges during post-exponential-growth phases, is independent of the characterized Upc2-pathway and is slower compared to the anaerobic uptake in S. cerevisiae and C. glabrata. Third, we observe under normoxic conditions in C. glabrata that Upc2-dependent sterol import can be induced in the presence of fetal bovine serum together with fluconazole. In summary, C. glabrata imports sterols both in aerobic and anaerobic conditions, and the limited aerobic uptake can be further stimulated by the presence of serum together with fluconazole. S. cerevisiae imports sterols only in anaerobic conditions, demonstrating aerobic sterol exclusion. Finally, C. albicans imports sterols exclusively aerobically in post-exponential-growth phases, independent of Upc2. For the first time, we provide direct evidence of sterol import into the human fungal pathogen C. albicans, which until now was believed to be incapable of active sterol import.

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“…However, the following is widely admitted: (a) most of the ERG genes are regulated by oxygen; (b) endogenous or exogenous sterols are regulators of gene expression (including ERG genes) through still unknown molecular mechanisms; (c) some sterols can inhibit several enzymatic steps of the sterol pathway; and (d) the regulatory process may depend on the sterol requirement for growth and on the presence of other lipids. The roles and the intracellular traffic of sterols have been extensively discussed 44,105,114,134,155,196,211 (for review, see ref. 43).…”

Section: Sterol Biosynthesismentioning

confidence: 99%

Role of the non‐respiratory pathways in the utilization of molecular oxygen by Saccharomyces cerevisiae

Rosenfeld

Beauvoit

2003

Yeast

133

110

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Saccharomyces cerevisiae is a facultative anaerobe devoid of mitochondrial alternative oxidase. In this yeast, the structure and biogenesis of the respiratory chain, on the one hand, and the functional interactions of oxidative phosphorylation with the cellular energetic metabolism, on the other, are well documented. However, to our knowledge, the molecular aspects and the physiological roles of the non-respiratory pathways that utilize molecular oxygen have not yet been reviewed. In this paper, we review the various non-respiratory pathways in a global context of utilization of molecular oxygen in S. cerevisiae. The roles of these pathways are examined as a function of environmental conditions, using either physiological, biochemical or molecular data. Special attention is paid to the characterization of the so-called 'cyanide-resistant respiration' that is induced by respiratory deficiency, catabolic repression and oxygen limitation during growth. Finally, several aspects of oxygen sensing are discussed.

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Anaerobiosis induces complex changes in sterol esterification pattern in the yeast Saccharomyces cerevisiae

Cited by 23 publications

References 11 publications

Transcriptional Regulation of the Two Sterol Esterification Genes in the Yeast Saccharomyces cerevisiae

Transcriptional Regulation of the Two Sterol Esterification Genes in the Yeast Saccharomyces cerevisiae

Comparison of Sterol Import under Aerobic and Anaerobic Conditions in Three Fungal Species, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae

Role of the non‐respiratory pathways in the utilization of molecular oxygen by Saccharomyces cerevisiae

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