Optical control of sphingolipid biosynthesis using photoswitchable sphingosines
Sphingolipid metabolism comprises a complex interconnected web of enzymes, metabolites, and modes of regulation that influence a wide range of cellular and physiological processes. Deciphering the biological relevance of this network is challenging as numerous intermediates of sphingolipid metabolis...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227524002293 |
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| author | Matthijs Kol Alexander J.E. Novak Johannes Morstein Christian Schröer Tolulope Sokoya Svenja Mensing Sergei M. Korneev Dirk Trauner Joost C.M. Holthuis |
| author_facet | Matthijs Kol Alexander J.E. Novak Johannes Morstein Christian Schröer Tolulope Sokoya Svenja Mensing Sergei M. Korneev Dirk Trauner Joost C.M. Holthuis |
| author_sort | Matthijs Kol |
| collection | DOAJ |
| description | Sphingolipid metabolism comprises a complex interconnected web of enzymes, metabolites, and modes of regulation that influence a wide range of cellular and physiological processes. Deciphering the biological relevance of this network is challenging as numerous intermediates of sphingolipid metabolism are short-lived molecules with often opposing biological activities. Here, we introduce clickable, azobenzene-containing sphingosines, termed caSphs, as light-sensitive substrates for sphingolipid biosynthesis. Photo-isomerization of the azobenzene moiety enables reversible switching between a straight trans- and curved cis-form of the lipid’s hydrocarbon tail. Combining in vitro enzyme assays with metabolic labeling studies, we demonstrate that trans-to-cis isomerization of caSphs profoundly stimulates their metabolic conversion by ceramide synthases and downstream sphingomyelin synthases. These light-induced changes in sphingolipid production rates are acute, reversible, and can be implemented with great efficiency in living cells. Our findings establish caSphs as versatile tools for manipulating sphingolipid biosynthesis and function with the spatiotemporal precision of light. |
| format | Article |
| id | doaj-art-b44ab56076874d33a96331948d0afc35 |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-b44ab56076874d33a96331948d0afc352025-01-30T05:12:40ZengElsevierJournal of Lipid Research0022-22752025-01-01661100724Optical control of sphingolipid biosynthesis using photoswitchable sphingosinesMatthijs Kol0Alexander J.E. Novak1Johannes Morstein2Christian Schröer3Tolulope Sokoya4Svenja Mensing5Sergei M. Korneev6Dirk Trauner7Joost C.M. Holthuis8Molecular Cell Biology Division, Department of Biology/Chemistry, Osnabrück University, Osnabrück, Germany; Center for Cellular Nanoanalytics, Osnabrück University, Osnabrück, Germany; For correspondence: Matthijs Kol; Dirk Trauner; Joost C. M. HolthuisDepartment of Chemistry, New York University, New York, New York, USADivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USAMolecular Cell Biology Division, Department of Biology/Chemistry, Osnabrück University, Osnabrück, Germany; Center for Cellular Nanoanalytics, Osnabrück University, Osnabrück, GermanyMolecular Cell Biology Division, Department of Biology/Chemistry, Osnabrück University, Osnabrück, Germany; Center for Cellular Nanoanalytics, Osnabrück University, Osnabrück, GermanyMolecular Cell Biology Division, Department of Biology/Chemistry, Osnabrück University, Osnabrück, Germany; Center for Cellular Nanoanalytics, Osnabrück University, Osnabrück, GermanyMolecular Cell Biology Division, Department of Biology/Chemistry, Osnabrück University, Osnabrück, Germany; Center for Cellular Nanoanalytics, Osnabrück University, Osnabrück, GermanyDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA; For correspondence: Matthijs Kol; Dirk Trauner; Joost C. M. HolthuisMolecular Cell Biology Division, Department of Biology/Chemistry, Osnabrück University, Osnabrück, Germany; Center for Cellular Nanoanalytics, Osnabrück University, Osnabrück, Germany; For correspondence: Matthijs Kol; Dirk Trauner; Joost C. M. HolthuisSphingolipid metabolism comprises a complex interconnected web of enzymes, metabolites, and modes of regulation that influence a wide range of cellular and physiological processes. Deciphering the biological relevance of this network is challenging as numerous intermediates of sphingolipid metabolism are short-lived molecules with often opposing biological activities. Here, we introduce clickable, azobenzene-containing sphingosines, termed caSphs, as light-sensitive substrates for sphingolipid biosynthesis. Photo-isomerization of the azobenzene moiety enables reversible switching between a straight trans- and curved cis-form of the lipid’s hydrocarbon tail. Combining in vitro enzyme assays with metabolic labeling studies, we demonstrate that trans-to-cis isomerization of caSphs profoundly stimulates their metabolic conversion by ceramide synthases and downstream sphingomyelin synthases. These light-induced changes in sphingolipid production rates are acute, reversible, and can be implemented with great efficiency in living cells. Our findings establish caSphs as versatile tools for manipulating sphingolipid biosynthesis and function with the spatiotemporal precision of light.http://www.sciencedirect.com/science/article/pii/S0022227524002293azobenzenebudding yeastcell-free expressionceramide synthasechemical synthesisclick chemistry |
| spellingShingle | Matthijs Kol Alexander J.E. Novak Johannes Morstein Christian Schröer Tolulope Sokoya Svenja Mensing Sergei M. Korneev Dirk Trauner Joost C.M. Holthuis Optical control of sphingolipid biosynthesis using photoswitchable sphingosines Journal of Lipid Research azobenzene budding yeast cell-free expression ceramide synthase chemical synthesis click chemistry |
| title | Optical control of sphingolipid biosynthesis using photoswitchable sphingosines |
| title_full | Optical control of sphingolipid biosynthesis using photoswitchable sphingosines |
| title_fullStr | Optical control of sphingolipid biosynthesis using photoswitchable sphingosines |
| title_full_unstemmed | Optical control of sphingolipid biosynthesis using photoswitchable sphingosines |
| title_short | Optical control of sphingolipid biosynthesis using photoswitchable sphingosines |
| title_sort | optical control of sphingolipid biosynthesis using photoswitchable sphingosines |
| topic | azobenzene budding yeast cell-free expression ceramide synthase chemical synthesis click chemistry |
| url | http://www.sciencedirect.com/science/article/pii/S0022227524002293 |
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