Ergosterol regulates sterol regulatory element binding protein (SREBP) cleavage in fission yeast.
Open accessAbstract
In fission yeast, the endoplasmic reticulum membrane-bound proteins Sre1 and Scp1, orthologs of mammalian sterol regulatory element binding protein (SREBP) and Scap, monitor sterol synthesis as an indirect measure of oxygen supply. When cellular oxygen levels are low, sterol synthesis is inhibited, and the Sre1-Scp1 complex responds by increasing transcription of genes required for adaptation to hypoxia. Sre1 and Scp1 are believed to detect a blockage in sterol synthesis by monitoring levels of particular sterols, but the evidence concerning which sterol signals this condition is unclear. Here, we demonstrate that Sre1-Scp1 senses ergosterol. Processing experimental data with a mathematical model of Sre1 and Scp1 function reveals a clear quantitative relationship between ergosterol concentration in the endoplasmic reticulum and Sre1 activation. Based on this relationship, we predict that the Sre1-Scp1 complex exists under "active" and "inactive" states and that the transition between these states is cooperatively mediated by ergosterol.
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All above lines of evidence suggest that ergosterol depletion resulted from azole stress might be a cause for the transcriptional responses by ergosterol biosynthesis genes, but some direct experimental data in other fungi are still required for making a definite conclusion.
“All above lines of evidence suggest that ergosterol depletion resulted from azole stress might be a cause for the transcriptional responses by ergosterol biosynthesis genes, but some direct experimental data in other fungi are still required for making a definite conclusion.”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Porter et al., 2010
Several lines of evidence suggest that ergosterol depletion might be a cause of azole-activated transcriptional responses by ergosterol biosynthesis genes.
“For azole-activated transcriptional responses by genes for ergosterol biosynthesis, several lines of evidence suggest that ergosterol depletion might be a cause.”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Porter et al., 2010
In S. pombe, ergosterol depletion activated the expression of ergosterol biosynthesis genes and their regulator Sre1p.
“In Schizosaccharomyces pombe, it was reported that ergosterol depletion activated the expression of ergosterol biosynthesis genes and their regulator Sre1p (Hughes et al., 2005; Porter et al., 2010).”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Porter et al., 2010
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- Authors
- Porter, J. R., Burg, J. S., Espenshade, P. J., & Iglesias, P. A.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Espenshade, Peter J.
- Iglesias, Pablo A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 285
- Issue
- 52
- Pages
- 41051-41061
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3003404
- OpenAlex
- W2083385012
- Cited by
- 36
- References
- 32
- Citations by year
- 2025: 5 · 2023: 1 · 2021: 3 · 2020: 1 · 2018: 2 · 2017: 7 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 5
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Texas Tech University
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL077588, HL 077588)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK079637)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- ergosterol, SREBP, SCP1, SCAP, endoplasmic reticulum, hypoxia, sterol biosynthesis, oxygen sensing, protein activation, cooperativity, mathematical model, Schizosaccharomyces pombe
- MeSH terms
- Endoplasmic Reticulum, Ergosterol, Humans, Microfilament Proteins, Models, Biological, Schizosaccharomyces, Signal Transduction, Response Elements, Schizosaccharomyces pombe Proteins
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