論文 - 詳細
| RRC ID | 88109 |
|---|---|
| 著者 | Li Q, Zhou X, Zhang X, Zhang C, Zhang SO. |
| タイトル | Nuclear receptor signaling regulates compartmentalized phosphatidylcholine remodeling to facilitate thermosensitive lipid droplet fusion. |
| ジャーナル | Nat Commun |
| Abstract |
Lipid droplet (LD) fusion plays a key role in cellular fat storage. How the phospholipid monolayer membrane of LD functions in fusion, however, is poorly understood. In Caenorhabditis elegans, loss of cytochrome P450 protein CYP-37A1 causes de-repression of nuclear receptor DAF-12, promoting thermosensitive LD fusion. Here, we report that in cyp-37A1 mutants, DAF-12 up-regulates the transcription and LD localization of seven fatty acid desaturases (FAT-1 to FAT-7) and a lysophosphatidylcholine acyltransferase 3 (LPCAT3) homolog MBOA-6. LD-targeting of these enzymes increases phosphatidylcholine (PC) containing ω-3 C20 polyunsaturated fatty acids, which are essential for thermosensitive fusion. ω-3 C20-PC increase LD membrane fluidity, as does high ambient temperature. Lowering LD membrane fluidity by a chemical membrane rigidifier attenuates thermosensitive fusion; ectopic targeting of ω3 desaturase FAT-1 or MBOA-6 to LDs increases fusion kinetics and thermosensitivity. Furthermore, human LPCAT3 localizes to LDs, positively regulates LD size in human cells and facilitates thermosensitive fusion in C. elegans. These results demonstrate that DAF-12 signaling regulates compartmentalized membrane remodeling and fluidization to facilitate conserved thermosensitive LD fusion. |
| 巻・号 | 16(1) |
| ページ | 3955 |
| 公開日 | 2025-4-27 |
| DOI | 10.1038/s41467-025-59256-6 |
| PII | 10.1038/s41467-025-59256-6 |
| PMID | 40289189 |
| PMC | PMC12034805 |
| MeSH | 1-Acylglycerophosphocholine O-Acyltransferase / genetics 1-Acylglycerophosphocholine O-Acyltransferase / metabolism Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cytochrome P-450 Enzyme System / genetics Cytochrome P-450 Enzyme System / metabolism Fatty Acid Desaturases / genetics Fatty Acid Desaturases / metabolism Humans Lipid Droplets* / metabolism Membrane Fluidity Membrane Fusion Phosphatidylcholines* / metabolism Receptors, Cytoplasmic and Nuclear* / genetics Receptors, Cytoplasmic and Nuclear* / metabolism Signal Transduction |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm583 tm420 tm331 tm2464 tm1655 tm2967 |