Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane
Abstract The nuclear envelope is a specialized subdomain of the endoplasmic reticulum and comprises the inner and outer nuclear membranes. Despite the crucial role of the inner nuclear membrane in genome regulation, its lipid metabolism remains poorly understood. Phosphatidic acid (PA) is essential...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54811-z |
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| author | Anete Romanauska Edvinas Stankunas Maya Schuldiner Alwin Köhler |
| author_facet | Anete Romanauska Edvinas Stankunas Maya Schuldiner Alwin Köhler |
| author_sort | Anete Romanauska |
| collection | DOAJ |
| description | Abstract The nuclear envelope is a specialized subdomain of the endoplasmic reticulum and comprises the inner and outer nuclear membranes. Despite the crucial role of the inner nuclear membrane in genome regulation, its lipid metabolism remains poorly understood. Phosphatidic acid (PA) is essential for membrane growth as well as lipid storage. Using a genome-wide lipid biosensor screen in S. cerevisiae, we identify regulators of inner nuclear membrane PA homeostasis, including yeast Seipin, a known mediator of nuclear lipid droplet biogenesis. Here, we show that Seipin preserves nuclear envelope integrity by preventing its deformation and ectopic membrane formation. Mutations of specific regions of Seipin, some linked to human lipodystrophy, disrupt PA distribution at the inner nuclear membrane and nuclear lipid droplet formation. Investigating the Seipin co-factor Ldb16 reveals that a triacylglycerol binding site is crucial for lipid droplet formation, whereas PA regulation can be functionally separated. Our study highlights the potential of lipid biosensor screens for examining inner nuclear membrane lipid metabolism. |
| format | Article |
| id | doaj-art-33a363b2bf4d4162a5b440976abae7c6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-33a363b2bf4d4162a5b440976abae7c62024-12-08T12:36:09ZengNature PortfolioNature Communications2041-17232024-12-0115111610.1038/s41467-024-54811-zSeipin governs phosphatidic acid homeostasis at the inner nuclear membraneAnete Romanauska0Edvinas Stankunas1Maya Schuldiner2Alwin Köhler3Max Perutz Labs, Vienna BioCenter Campus (VBC), Dr. Bohr-Gasse 9/3Max Perutz Labs, Vienna BioCenter Campus (VBC), Dr. Bohr-Gasse 9/3Department of Molecular Genetics, Weizmann Institute of ScienceMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr. Bohr-Gasse 9/3Abstract The nuclear envelope is a specialized subdomain of the endoplasmic reticulum and comprises the inner and outer nuclear membranes. Despite the crucial role of the inner nuclear membrane in genome regulation, its lipid metabolism remains poorly understood. Phosphatidic acid (PA) is essential for membrane growth as well as lipid storage. Using a genome-wide lipid biosensor screen in S. cerevisiae, we identify regulators of inner nuclear membrane PA homeostasis, including yeast Seipin, a known mediator of nuclear lipid droplet biogenesis. Here, we show that Seipin preserves nuclear envelope integrity by preventing its deformation and ectopic membrane formation. Mutations of specific regions of Seipin, some linked to human lipodystrophy, disrupt PA distribution at the inner nuclear membrane and nuclear lipid droplet formation. Investigating the Seipin co-factor Ldb16 reveals that a triacylglycerol binding site is crucial for lipid droplet formation, whereas PA regulation can be functionally separated. Our study highlights the potential of lipid biosensor screens for examining inner nuclear membrane lipid metabolism.https://doi.org/10.1038/s41467-024-54811-z |
| spellingShingle | Anete Romanauska Edvinas Stankunas Maya Schuldiner Alwin Köhler Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane Nature Communications |
| title | Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane |
| title_full | Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane |
| title_fullStr | Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane |
| title_full_unstemmed | Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane |
| title_short | Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane |
| title_sort | seipin governs phosphatidic acid homeostasis at the inner nuclear membrane |
| url | https://doi.org/10.1038/s41467-024-54811-z |
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