論文 - 詳細
| RRC ID | 87340 |
|---|---|
| 著者 | Hoshikawa Y, Shirota N, Tsugawa H, Kimura S, Matsuyama A, Yashiroda Y, Kakeya H, Arita M, Iizumi R, Yoshida M, Nishimura S. |
| タイトル | Formation of giant ER sheets by pentadecanoic acid causes lipotoxicity in fission yeast. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Excess amounts of saturated fatty acids (FAs) are toxic to organisms, a condition termed lipotoxicity, which is often accompanied by pleiotropic cellular and tissue dysfunction. Here, we show that pentadecanoic acid (C15:0) exerts toxicity on the fission yeast Schizosaccharomyces pombe by generating an aberrantly planar endoplasmic reticulum (ER) structure, which we named a "giant ER sheet." Untargeted lipidomics revealed that C15:0 is incorporated into complex lipids depending on an acyl-CoA ligase Lcf1 and an acyl-CoA transferase Slc1, thereby increasing the saturation level of the acyl chains. The toxicity and giant ER sheet formation were abolished by deleting lcf1 or slc1 gene, indicating that the incorporation of C15:0 into glycerophospholipids causes giant ER sheet formation. The giant ER sheets disrupted the correct migration of Mid1, a protein determining the cell division site, and physically blocked septum formation, hindering correct cell separation. Our results suggest that the ER is the primary site targeted by saturated FAs, leading to lipotoxicity. |
| 巻・号 | 122(22) |
| ページ | e2422126122 |
| 公開日 | 2025-6-3 |
| DOI | 10.1073/pnas.2422126122 |
| PMID | 40424131 |
| PMC | PMC12146749 |
| MeSH | Coenzyme A Ligases / genetics Coenzyme A Ligases / metabolism Endoplasmic Reticulum* / drug effects Endoplasmic Reticulum* / metabolism Fatty Acids* / metabolism Fatty Acids* / toxicity Lipidomics Schizosaccharomyces* / drug effects Schizosaccharomyces* / genetics Schizosaccharomyces* / metabolism Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism |
| IF | 9.412 |
| 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 | 15 |
| 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 | |
| 酵母 | FY16936 FY16937 |