Human Sterols Are Overproduced, Stored and Excreted in Yeasts
Sterols exert a profound influence on numerous cellular processes, playing a crucial role in both health and disease. However, comprehending the effects of sterol dysfunction on cellular physiology is challenging. Consequently, numerous processes affected by impaired sterol biosynthesis still elude...
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/781 |
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| author | Astrid Radkohl Veronika Schusterbauer Lukas Bernauer Gerald N. Rechberger Heimo Wolinski Matthias Schittmayer Ruth Birner-Gruenberger Gerhard G. Thallinger Erich Leitner Melanie Baeck Harald Pichler Anita Emmerstorfer-Augustin |
| author_facet | Astrid Radkohl Veronika Schusterbauer Lukas Bernauer Gerald N. Rechberger Heimo Wolinski Matthias Schittmayer Ruth Birner-Gruenberger Gerhard G. Thallinger Erich Leitner Melanie Baeck Harald Pichler Anita Emmerstorfer-Augustin |
| author_sort | Astrid Radkohl |
| collection | DOAJ |
| description | Sterols exert a profound influence on numerous cellular processes, playing a crucial role in both health and disease. However, comprehending the effects of sterol dysfunction on cellular physiology is challenging. Consequently, numerous processes affected by impaired sterol biosynthesis still elude our complete understanding. In this study, we made use of yeast strains that produce cholesterol instead of ergosterol and investigated the cellular response mechanisms on the transcriptome as well as the lipid level. The exchange of ergosterol for cholesterol caused the downregulation of phosphatidylethanolamine and phosphatidylserine and upregulation of phosphatidylinositol and phosphatidylcholine biosynthesis. Additionally, a shift towards polyunsaturated fatty acids was observed. While the sphingolipid levels dropped, the total amounts of sterols and triacylglycerol increased, which resulted in 1.7-fold enlarged lipid droplets in cholesterol-producing yeast cells. In addition to internal storage, cholesterol and its precursors were excreted into the culture supernatant, most likely by the action of ABC transporters Snq2, Pdr12 and Pdr15. Overall, our results demonstrate that, similarly to mammalian cells, the production of non-native sterols and sterol precursors causes lipotoxicity in <i>K. phaffii</i>, mainly due to upregulated sterol biosynthesis, and they highlight the different survival and stress response mechanisms on multiple, integrative levels. |
| first_indexed | 2024-03-08T09:54:03Z |
| format | Article |
| id | doaj.art-9f37d800c6c54ada9766c6122ac225f0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:54:03Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9f37d800c6c54ada9766c6122ac225f02024-01-29T13:54:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125278110.3390/ijms25020781Human Sterols Are Overproduced, Stored and Excreted in YeastsAstrid Radkohl0Veronika Schusterbauer1Lukas Bernauer2Gerald N. Rechberger3Heimo Wolinski4Matthias Schittmayer5Ruth Birner-Gruenberger6Gerhard G. Thallinger7Erich Leitner8Melanie Baeck9Harald Pichler10Anita Emmerstorfer-Augustin11Institute of Molecular Biotechnology, Graz University of Technology, NAWI Graz, 8010 Graz, AustriaBisy GmbH, 8200 Hofstaetten an der Raab, AustriaInstitute of Molecular Biotechnology, Graz University of Technology, NAWI Graz, 8010 Graz, AustriaDepartment of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, AustriaDepartment of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, AustriaInstitute of Chemical Technologies and Analytics, Technische Universität Wien, 1040 Vienna, AustriaInstitute of Chemical Technologies and Analytics, Technische Universität Wien, 1040 Vienna, AustriaInstitute of Biomedical Informatics, Graz University of Technology, 8010 Graz, AustriaInstitute of Analytical Chemistry and Food Chemistry, University of Graz, NAWI Graz, 8010 Graz, AustriaInstitute of Molecular Biotechnology, Graz University of Technology, NAWI Graz, 8010 Graz, AustriaInstitute of Molecular Biotechnology, Graz University of Technology, NAWI Graz, 8010 Graz, AustriaInstitute of Molecular Biotechnology, Graz University of Technology, NAWI Graz, 8010 Graz, AustriaSterols exert a profound influence on numerous cellular processes, playing a crucial role in both health and disease. However, comprehending the effects of sterol dysfunction on cellular physiology is challenging. Consequently, numerous processes affected by impaired sterol biosynthesis still elude our complete understanding. In this study, we made use of yeast strains that produce cholesterol instead of ergosterol and investigated the cellular response mechanisms on the transcriptome as well as the lipid level. The exchange of ergosterol for cholesterol caused the downregulation of phosphatidylethanolamine and phosphatidylserine and upregulation of phosphatidylinositol and phosphatidylcholine biosynthesis. Additionally, a shift towards polyunsaturated fatty acids was observed. While the sphingolipid levels dropped, the total amounts of sterols and triacylglycerol increased, which resulted in 1.7-fold enlarged lipid droplets in cholesterol-producing yeast cells. In addition to internal storage, cholesterol and its precursors were excreted into the culture supernatant, most likely by the action of ABC transporters Snq2, Pdr12 and Pdr15. Overall, our results demonstrate that, similarly to mammalian cells, the production of non-native sterols and sterol precursors causes lipotoxicity in <i>K. phaffii</i>, mainly due to upregulated sterol biosynthesis, and they highlight the different survival and stress response mechanisms on multiple, integrative levels.https://www.mdpi.com/1422-0067/25/2/781cholesterolergosterol<i>Komagataella phaffii</i><i>Pichia pastoris</i>yeastplasma membrane |
| spellingShingle | Astrid Radkohl Veronika Schusterbauer Lukas Bernauer Gerald N. Rechberger Heimo Wolinski Matthias Schittmayer Ruth Birner-Gruenberger Gerhard G. Thallinger Erich Leitner Melanie Baeck Harald Pichler Anita Emmerstorfer-Augustin Human Sterols Are Overproduced, Stored and Excreted in Yeasts International Journal of Molecular Sciences cholesterol ergosterol <i>Komagataella phaffii</i> <i>Pichia pastoris</i> yeast plasma membrane |
| title | Human Sterols Are Overproduced, Stored and Excreted in Yeasts |
| title_full | Human Sterols Are Overproduced, Stored and Excreted in Yeasts |
| title_fullStr | Human Sterols Are Overproduced, Stored and Excreted in Yeasts |
| title_full_unstemmed | Human Sterols Are Overproduced, Stored and Excreted in Yeasts |
| title_short | Human Sterols Are Overproduced, Stored and Excreted in Yeasts |
| title_sort | human sterols are overproduced stored and excreted in yeasts |
| topic | cholesterol ergosterol <i>Komagataella phaffii</i> <i>Pichia pastoris</i> yeast plasma membrane |
| url | https://www.mdpi.com/1422-0067/25/2/781 |
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