类胆协调了ER-自主和ER-非自主适应对未展开的蛋白质反应功能障碍的适应
Haixiang Tong1, Wei Li1, Pangui Yuan1
1School of Life Sciences, Chongqing University, Chongqing, China.
The Journal of biological chemistry
|December 8, 2025
概括
细胞应激反应通过激活ER-自主和ER-非自主通路来适应内质网膜未折叠蛋白响应 (UPR) 缺陷. 类胆代谢将ER UPR功能与溶酶体活性联系起来,促进长寿.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
背景情况:
- 细胞内膜网膜未展开的蛋白质反应 (ER UPR) 对于维持蛋白质稳定至关重要.
- ER UPR 功能障碍与衰老和各种疾病有关.
- 应对ER UPR功能障碍的细胞机制尚未完全理解.
研究的目的:
- 调查IRE1/XBP1 UPR分支中的缺陷的适应性反应.
- 阐明酸丁胆 (PC) 代谢在蛋白质稳定中的作用.
- 了解细胞如何在受损的ER UPR条件下维持蛋白质稳定.
主要方法:
- 使用Caenorhabditis elegans作为一个模型生物.
- 调查了 IRE1/XBP1 和 PEK1 UPR 分支.
- 分析了酸丁胆代谢和 lysosomal 功能.
主要成果:
- IRE1/XBP1功能障碍激活了PEK1 UPR分支和依赖于溶酶体的细胞质蛋白质静止反应.
- IRE1/XBP1功能障碍导致酸丁胆水平降低,引发了 lysosomal 激活.
- 仅抑制酸丁胆代谢就激活了ER UPR和溶酶体通路,增强了应激抵抗力和寿命.
结论:
- 细胞使用集成的ER-自主和ER-非自主反应来维持ER UPR功能障碍期间的蛋白质静止.
- 类胆代谢是连接ER UPR, lysosomal活动和系统性蛋白质稳定性的关键调节器.
- 向酸丁胆代谢可能提供提高对蛋白质稳定性压力的弹性和促进健康衰老的策略.
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