論文 - 詳細
| RRC ID | 76222 |
|---|---|
| 著者 | Li X, Li J, Zhu D, Zhang N, Hao X, Zhang W, Zhang Q, Liu Y, Wu X, Tian Y. |
| タイトル | Protein disulfide isomerase PDI-6 regulates Wnt secretion to coordinate inter-tissue UPRmt activation and lifespan extension in C. elegans. |
| ジャーナル | Cell Rep |
| Abstract |
Coordination of inter-tissue stress signaling is essential for organismal fitness. Neuronal mitochondrial perturbations activate the mitochondrial unfolded-protein response (UPRmt) in the intestine via the mitokine Wnt signaling in Caenorhabditis elegans. Here, we found that the protein disulfide isomerase PDI-6 coordinates inter-tissue UPRmt signaling via regulating the Wnt ligand EGL-20. PDI-6 is expressed in the endoplasmic reticulum (ER) and interacts with EGL-20 through disulfide bonds that are essential for EGL-20 stability and secretion. pdi-6 deficiency results in misfolded EGL-20, which leads to its degradation via ER-associated protein degradation (ERAD) machinery. Expression of PDI-6 declines drastically with aging, and animals with pdi-6 deficiency have decreased lifespan. Overexpression of PDI-6 is sufficient to maintain Wnt/EGL-20 protein levels during aging, activating the UPRmt, and significantly extending lifespan in a Wnt- and UPRmt-dependent manner. Our study reveals that protein disulfide isomerase facilitates Wnt secretion to coordinate the inter-tissue UPRmt signaling and organismal aging. |
| 巻・号 | 39(10) |
| ページ | 110931 |
| 公開日 | 2022-6-7 |
| DOI | 10.1016/j.celrep.2022.110931 |
| PII | S2211-1247(22)00713-6 |
| PMID | 35675782 |
| MeSH | Animals Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Longevity Protein Disulfide-Isomerases / genetics Protein Disulfide-Isomerases / metabolism Unfolded Protein Response Wnt Proteins / metabolism |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 13 |
| 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 | tm2482 |