Sterol Metabolism Differentially Contributes to Maintenance and Exit of Quiescence
Nutrient starvation initiates cell cycle exit and entry into quiescence, a reversible, non-proliferative state characterized by stress tolerance, longevity and large-scale remodeling of subcellular structures. Depending on the nature of the depleted nutrient, yeast cells are assumed to enter heterog...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.788472/full |
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| author | Carlotta Peselj Mahsa Ebrahimi Filomena Broeskamp Simon Prokisch Lukas Habernig Irene Alvarez-Guerra Verena Kohler F.-Nora Vögtle F.-Nora Vögtle F.-Nora Vögtle Sabrina Büttner Sabrina Büttner |
| author_facet | Carlotta Peselj Mahsa Ebrahimi Filomena Broeskamp Simon Prokisch Lukas Habernig Irene Alvarez-Guerra Verena Kohler F.-Nora Vögtle F.-Nora Vögtle F.-Nora Vögtle Sabrina Büttner Sabrina Büttner |
| author_sort | Carlotta Peselj |
| collection | DOAJ |
| description | Nutrient starvation initiates cell cycle exit and entry into quiescence, a reversible, non-proliferative state characterized by stress tolerance, longevity and large-scale remodeling of subcellular structures. Depending on the nature of the depleted nutrient, yeast cells are assumed to enter heterogeneous quiescent states with unique but mostly unexplored characteristics. Here, we show that storage and consumption of neutral lipids in lipid droplets (LDs) differentially impacts the regulation of quiescence driven by glucose or phosphate starvation. Upon prolonged glucose exhaustion, LDs were degraded in the vacuole via Atg1-dependent lipophagy. In contrast, yeast cells entering quiescence due to phosphate exhaustion massively over-accumulated LDs that clustered at the vacuolar surface but were not engulfed via lipophagy. Excessive LD biogenesis required contact formation between the endoplasmic reticulum and the vacuole at nucleus-vacuole junctions and was accompanied by a shift of the cellular lipid profile from membrane towards storage lipids, driven by a transcriptional upregulation of enzymes generating neutral lipids, in particular sterol esters. Importantly, sterol ester biogenesis was critical for long-term survival of phosphate-exhausted cells and supported rapid quiescence exit upon nutrient replenishment, but was dispensable for survival and regrowth of glucose-exhausted cells. Instead, these cells relied on de novo synthesis of sterols and fatty acids for quiescence exit and regrowth. Phosphate-exhausted cells efficiently mobilized storage lipids to support several rounds of cell division even in presence of inhibitors of fatty acid and sterol biosynthesis. In sum, our results show that neutral lipid biosynthesis and mobilization to support quiescence maintenance and exit is tailored to the respective nutrient scarcity. |
| first_indexed | 2024-12-13T13:01:48Z |
| format | Article |
| id | doaj.art-4d0b1f8ac67b4bb5acd059d5aa24532d |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T13:01:48Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-4d0b1f8ac67b4bb5acd059d5aa24532d2022-12-21T23:44:58ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-02-011010.3389/fcell.2022.788472788472Sterol Metabolism Differentially Contributes to Maintenance and Exit of QuiescenceCarlotta Peselj0Mahsa Ebrahimi1Filomena Broeskamp2Simon Prokisch3Lukas Habernig4Irene Alvarez-Guerra5Verena Kohler6F.-Nora Vögtle7F.-Nora Vögtle8F.-Nora Vögtle9Sabrina Büttner10Sabrina Büttner11Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenCenter for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg University, Heidelberg, GermanyNetwork Aging Research, Heidelberg University, Heidelberg, GermanyCIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, GermanyDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenInstitute of Molecular Biosciences, University of Graz, Graz, AustriaNutrient starvation initiates cell cycle exit and entry into quiescence, a reversible, non-proliferative state characterized by stress tolerance, longevity and large-scale remodeling of subcellular structures. Depending on the nature of the depleted nutrient, yeast cells are assumed to enter heterogeneous quiescent states with unique but mostly unexplored characteristics. Here, we show that storage and consumption of neutral lipids in lipid droplets (LDs) differentially impacts the regulation of quiescence driven by glucose or phosphate starvation. Upon prolonged glucose exhaustion, LDs were degraded in the vacuole via Atg1-dependent lipophagy. In contrast, yeast cells entering quiescence due to phosphate exhaustion massively over-accumulated LDs that clustered at the vacuolar surface but were not engulfed via lipophagy. Excessive LD biogenesis required contact formation between the endoplasmic reticulum and the vacuole at nucleus-vacuole junctions and was accompanied by a shift of the cellular lipid profile from membrane towards storage lipids, driven by a transcriptional upregulation of enzymes generating neutral lipids, in particular sterol esters. Importantly, sterol ester biogenesis was critical for long-term survival of phosphate-exhausted cells and supported rapid quiescence exit upon nutrient replenishment, but was dispensable for survival and regrowth of glucose-exhausted cells. Instead, these cells relied on de novo synthesis of sterols and fatty acids for quiescence exit and regrowth. Phosphate-exhausted cells efficiently mobilized storage lipids to support several rounds of cell division even in presence of inhibitors of fatty acid and sterol biosynthesis. In sum, our results show that neutral lipid biosynthesis and mobilization to support quiescence maintenance and exit is tailored to the respective nutrient scarcity.https://www.frontiersin.org/articles/10.3389/fcell.2022.788472/fulllipid dropletsmembrane contact sitesNVJyeastquiescencelipophagy |
| spellingShingle | Carlotta Peselj Mahsa Ebrahimi Filomena Broeskamp Simon Prokisch Lukas Habernig Irene Alvarez-Guerra Verena Kohler F.-Nora Vögtle F.-Nora Vögtle F.-Nora Vögtle Sabrina Büttner Sabrina Büttner Sterol Metabolism Differentially Contributes to Maintenance and Exit of Quiescence Frontiers in Cell and Developmental Biology lipid droplets membrane contact sites NVJ yeast quiescence lipophagy |
| title | Sterol Metabolism Differentially Contributes to Maintenance and Exit of Quiescence |
| title_full | Sterol Metabolism Differentially Contributes to Maintenance and Exit of Quiescence |
| title_fullStr | Sterol Metabolism Differentially Contributes to Maintenance and Exit of Quiescence |
| title_full_unstemmed | Sterol Metabolism Differentially Contributes to Maintenance and Exit of Quiescence |
| title_short | Sterol Metabolism Differentially Contributes to Maintenance and Exit of Quiescence |
| title_sort | sterol metabolism differentially contributes to maintenance and exit of quiescence |
| topic | lipid droplets membrane contact sites NVJ yeast quiescence lipophagy |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.788472/full |
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