論文 - 詳細
| RRC ID | 45728 |
|---|---|
| 著者 | Folick A, Oakley HD, Yu Y, Armstrong EH, Kumari M, Sanor L, Moore DD, Ortlund EA, Zechner R, Wang MC. |
| タイトル | Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans. |
| ジャーナル | Science |
| Abstract |
Lysosomes are crucial cellular organelles for human health that function in digestion and recycling of extracellular and intracellular macromolecules. We describe a signaling role for lysosomes that affects aging. In the worm Caenorhabditis elegans, the lysosomal acid lipase LIPL-4 triggered nuclear translocalization of a lysosomal lipid chaperone LBP-8, which promoted longevity by activating the nuclear hormone receptors NHR-49 and NHR-80. We used high-throughput metabolomic analysis to identify several lipids in which abundance was increased in worms constitutively overexpressing LIPL-4. Among them, oleoylethanolamide directly bound to LBP-8 and NHR-80 proteins, activated transcription of target genes of NHR-49 and NHR-80, and promoted longevity in C. elegans. These findings reveal a lysosome-to-nucleus signaling pathway that promotes longevity and suggest a function of lysosomes as signaling organelles in metazoans. |
| 巻・号 | 347(6217) |
| ページ | 83-6 |
| 公開日 | 2015-1-2 |
| DOI | 10.1126/science.1258857 |
| PII | 347/6217/83 |
| PMID | 25554789 |
| PMC | PMC4425353 |
| MeSH | Active Transport, Cell Nucleus Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / metabolism Lipase / metabolism Lipid Metabolism Longevity / genetics Longevity / physiology* Lysosomes / metabolism* Molecular Chaperones / genetics Molecular Chaperones / metabolism* Receptors, Cytoplasmic and Nuclear / metabolism Signal Transduction |
| IF | 41.846 |
| 引用数 | 109 |
| WOS 分野 | MULTIDISCIPLINARY SCIENCES |
| 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 | 155 |
| 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 | tm4417 tm1011 tm3860 |