曼诺斯代谢途径感知葡萄糖供应,并调节细胞命运决定
Ziwei Wang1, Yasuhide Miyamoto2, Takehiro Suzuki3
1Department of Glyco-Oncology and Medical Biochemistry, Osaka International Cancer Institute, Chuo-ku, Osaka, Japan; Department of Molecular Oncology, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.
The Journal of biological chemistry
|January 30, 2026
概括
细胞通过调整的代谢途径来控制自己的命运. 破坏这种途径会影响N-糖化和溶酶体完整性,从而影响细胞生存和死亡的决定.
科学领域:
- 细胞代谢的细胞代谢.
- 分子生物学分子生物学
- 细胞平衡是细胞的平衡.
背景情况:
- 哺乳动物细胞利用不同的代谢途径来调节细胞命运,特别是在缺乏葡萄糖期间.
- 以前,葡萄糖剥夺已被证明可以降低曼诺斯通路活性,影响N-糖化,并导致生物合成停止.
- 这种代谢反应的确切细胞作用仍然不清楚,因为缺乏葡萄糖的并发症.
研究的目的:
- 研究曼诺糖代谢途径在调节细胞命运中的细胞作用.
- 从糖溶解中剖析曼诺斯路径,以精确控制其活性.
- 了解改变曼诺斯通路流动对细胞过程的后果.
主要方法:
- 基因工程细胞分离曼诺路由从糖解.
- 通过调整曼诺斯供应水平来控制曼诺斯通路活动.
- 评估了N-糖化,PERK-eIF2信号,溶酶体完整性和细胞存活在不同的曼诺斯供应下.
主要成果:
- 适度减少曼诺斯供应抑制了N-糖化和激活了支持生存的PERK-eIF2信号.
- 最小的曼诺斯供应并没有影响细胞存活,但减少了 lysosomal glycocalyx,并通过损害 lysosome 完整性增加了细胞死亡风险.
- 这些发现将N-糖化缺陷与ER和溶酶体恒常度改变联系起来.
结论:
- 通过曼路径的低代谢流影响细胞命运决定.
- N-糖化缺陷和 lysosome 完整性是这些细胞命运结果的关键媒介.
- 曼诺糖通路在维持细胞平衡和调节生存方面发挥着至关重要的作用.
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