IDH1突变胶质瘤代谢偏好的研究
Research on the Metabolic Preferences of IDH1-Mutant Gliomas
王佳蓉 1陈冬1
作者信息
- 1. 苏州大学唐仲英医学研究院，苏州，215123
- 折叠
摘要
【目的】IDH1（Isocitrate Dehydrogenase 1）是异柠檬酸脱氢酶家族成员之一，负责催化异柠檬酸氧化脱羧生成酮戊二酸（Alpha-Ketoglutaric acid，α-KG）和NADPH，为细胞提供养分和还原当量。IDH1在胶质瘤细胞中存在突变体（mutant IDH1，mIDH1），其中最常见的类型为R132H型，与胶质瘤的发生发展密切相关。因此，我们旨在探讨IDH1 R132H突变对胶质瘤细胞代谢重编程的影响，明确mIDH1胶质瘤细胞的关键代谢依赖及潜在干预靶点。【方法】以U87MG细胞及U87MG IDH1R132H过表达细胞为研究模型，比较分析IDH1突变对胶质瘤细胞代谢表型的影响，重点评估谷氨酰胺代谢及其相关线粒体代谢过程在mIDH1胶质瘤细胞存活中的作用。【结果】与普通U87MG细胞相比，U87MG IDH1R132H过表达细胞对谷氨酰胺代谢表现出更强依赖性，尤其依赖谷氨酰胺转化为谷氨酸后进入线粒体的连续代谢过程。进一步分析显示，a-酮戊二酸和天冬酰胺能够为mIDH1胶质瘤细胞存活提供重要代谢支持，提示IDH1 R132H突变诱导胶质瘤细胞形成以线粒体代谢为核心的代谢依赖特征。【结论】IDH1 R132H突变可促进胶质瘤细胞发生代谢重编程，使其生存更依赖谷氨酰胺驱动的线粒体代谢通路。该研究揭示了mIDH1胶质瘤细胞线粒体代谢依赖的关键特征，为深入理解IDH1突变在胶质瘤发生发展中的作用提供了实验依据，并为mIDH1胶质瘤的代谢靶向治疗提供了潜在策略。
Abstract
Objective: IDH1 (isocitrate dehydrogenase 1) is a member of the isocitrate dehydrogenase family that catalyzes the oxidative decarboxylation of isocitrate to produce α-ketoglutarate (α-KG) and NADPH, thereby providing nutrients and reducing equivalents for cells. Mutant IDH1 (mIDH1) is frequently detected in glioma cells, among which the R132H mutation is the most common and is closely associated with glioma initiation and progression. Therefore, this study aimed to investigate the effects of the IDH1 R132H mutation on metabolic reprogramming in glioma cells and to identify the key metabolic dependencies and potential therapeutic targets of mIDH1 glioma cells. Methods: U87MG cells and U87MG cells overexpressing IDH1 R132H were used as experimental models. The effects of the IDH1 mutation on the metabolic phenotype of glioma cells were comparatively analyzed, with a particular focus on the role of glutamine metabolism and its related mitochondrial metabolic processes in the survival of mIDH1 glioma cells. Results: Compared with parental U87MG cells, U87MG cells overexpressing IDH1 R132H exhibited a greater dependence on glutamine metabolism, particularly on the sequential mitochondrial metabolic processes following the conversion of glutamine to glutamate. Further analyses demonstrated that α-ketoglutarate and asparagine provided essential metabolic support for the survival of mIDH1 glioma cells, suggesting that the IDH1 R132H mutation induces a metabolic dependency pattern centered on mitochondrial metabolism in glioma cells. Conclusion: The IDH1 R132H mutation promotes metabolic reprogramming in glioma cells, rendering their survival more dependent on glutamine-driven mitochondrial metabolic pathways. These findings reveal key features of mitochondrial metabolic dependency in mIDH1 glioma cells, provide experimental evidence for a deeper understanding of the role of IDH1 mutations in glioma development and progression, and offer potential strategies for metabolic-targeted therapy in mIDH1 glioma.关键词
IDH1/胶质瘤/肿瘤代谢Key words
IDH1/glioma/mitochondrial metabolism引用本文复制引用
王佳蓉,陈冬.IDH1突变胶质瘤代谢偏好的研究[EB/OL].(2026-05-08)[2026-05-10].http://www.paper.edu.cn/releasepaper/content/202605-3.学科分类
肿瘤学/基础医学
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