論文 - 詳細
| RRC ID | 81584 |
|---|---|
| 著者 | Etoh K, Araki H, Koga T, Hino Y, Kuribayashi K, Hino S, Nakao M. |
| タイトル | Citrate metabolism controls the senescent microenvironment via the remodeling of pro-inflammatory enhancers. |
| ジャーナル | Cell Rep |
| Abstract |
The senescent microenvironment and aged cells per se contribute to tissue remodeling, chronic inflammation, and age-associated dysfunction. However, the metabolic and epigenomic bases of the senescence-associated secretory phenotype (SASP) remain largely unknown. Here, we show that ATP-citrate lyase (ACLY), a key enzyme in acetyl-coenzyme A (CoA) synthesis, is essential for the pro-inflammatory SASP, independent of persistent growth arrest in senescent cells. Citrate-derived acetyl-CoA facilitates the action of SASP gene enhancers. ACLY-dependent de novo enhancers augment the recruitment of the chromatin reader BRD4, which causes SASP activation. Consistently, specific inhibitions of the ACLY-BRD4 axis suppress the STAT1-mediated interferon response, creating the pro-inflammatory microenvironment in senescent cells and tissues. Our results demonstrate that ACLY-dependent citrate metabolism represents a selective target for controlling SASP designed to promote healthy aging. |
| 巻・号 | 43(8) |
| ページ | 114496 |
| 公開日 | 2024-8-27 |
| DOI | 10.1016/j.celrep.2024.114496 |
| PII | S2211-1247(24)00825-8 |
| PMID | 39043191 |
| MeSH | ATP Citrate (pro-S)-Lyase* / genetics ATP Citrate (pro-S)-Lyase* / metabolism Acetyl Coenzyme A / metabolism Animals Cellular Microenvironment Cellular Senescence* Citric Acid* / metabolism Enhancer Elements, Genetic / genetics Humans Inflammation / metabolism Inflammation / pathology Mice Mice, Inbred C57BL Nuclear Proteins / metabolism Transcription Factors* / metabolism |
| IF | 8.109 |
| 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 | 56 |
| 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 | |
| 遺伝子材料 | pMRX-puro-EGFP-Rab6A (RDB17361) |