論文 - 詳細
| RRC ID | 88043 |
|---|---|
| 著者 | Kaper D, Radović U, Bergh PO, Qvist A, Henricsson M, Borén J, Pilon M. |
| タイトル | Forward genetics in C. elegans reveals genetic adaptations to polyunsaturated fatty acid deficiency. |
| ジャーナル | Elife |
| Abstract |
Polyunsaturated fatty acids (PUFAs) are essential for mammalian health and function as membrane fluidizers and precursors for signaling lipids, though the primary essential function of PUFAs within organisms has not been established. Unlike mammals who cannot endogenously synthesize PUFAs, C. elegans can de novo synthesize PUFAs starting with the Δ12 desaturase FAT-2, which introduces a second double bond to monounsaturated fatty acids to generate the PUFA linoleic acid. FAT-2 desaturation is essential for C. elegans survival since fat-2 null mutants are non-viable; the near-null fat-2(wa17) allele synthesizes only small amounts of PUFAs and produces extremely sick worms. Using fluorescence recovery after photobleaching (FRAP), we found that the fat-2(wa17) mutant has rigid membranes and can be efficiently rescued by dietarily providing various PUFAs, but not by fluidizing treatments or mutations. With the aim of identifying mechanisms that compensate for PUFA-deficiency, we performed a forward genetics screen to isolate novel fat-2(wa17) suppressors and identified four internal mutations within fat-2 and six mutations within the HIF-1 pathway. The suppressors increase PUFA levels in fat-2(wa17) mutant worms and additionally suppress the activation of the daf-16, UPRer and UPRmt stress response pathways that are active in fat-2(wa17) worms. We hypothesize that the six HIF-1 pathway mutations, found in egl-9, ftn-2, and hif-1, all converge on raising Fe2+ levels and in this way boost desaturase activity, including that of the fat-2(wa17) allele. We conclude that PUFAs cannot be genetically replaced and that the only genetic mechanism that can alleviate PUFA-deficiency do so by increasing PUFA levels. |
| 巻・号 | 13 |
| 公開日 | 2025-7-8 |
| DOI | 10.7554/eLife.104181 |
| PII | 104181 |
| PMID | 40627529 |
| PMC | PMC12237404 |
| MeSH | Adaptation, Physiological* Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans* / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Fatty Acid Desaturases / genetics Fatty Acid Desaturases / metabolism Fatty Acids, Unsaturated* / deficiency Fatty Acids, Unsaturated* / metabolism Mutation |
| 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 | Bluesky |
| 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 | tm3410 |