时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
We hypothesized that disulfide stress did not activate caspases because caspases undergo polymerization, similarly to actin cytoskeleton associated proteins, resulting in a loss of activity.；This ultimately led to NAD(P)H metabolic dysregulation and induced disulfidptosis in FHdeficient cells (Fig. 6M).Targeting complex I with metformin inhibits FHdeficient tumor growthNext, we aimed to investigate whether metformin could inhibit the growth of FHdeficient RCC in vivo.；Whether this cytoskeletal succination exerts an opposing effect (i.e., suppressing disulfidptosis) under lower succination loads or in specific cell types remains to be determined.
方法
In this study, we discovered that FHdeficient cells initiate disulfidptosis under glucose deprivation and elucidated the molecular basis for its caspase-independent nature.；Measurement of fumarate levels revealed that both 10 μM FH-IN1-treated HeLa cells, KD-FH 786-O cells, and FHdeficient UOK262 cells exhibited significant fumarate accumulation (Fig.；Next, we observed a time-dependent increase in cell death during glucose starvation across all models (Fig. 1A–F).
核心结论
These results demonstrated that glucose starvation induced cell death in FH-inactivated cells.；These results demonstrated that glucose starvation-induced death in FHdeficient cells was oxidants-independent.Disulfidptosis is triggered by NADPH depletion-induced collapse of the redox system, and this form of cell death can be rescued by 2-Deoxy-D-glucose (2DG) treatment7.；Further analysis using capillary electrophoresis-mass spectrometry (CE-MS) demonstrated that 2DG reduced glycolysis metabolite fructose-6-phosphate (F6P), while promoting the conversion of 2DG to 2-Deoxyglucose-6-phosphate (2DG-6P) (Fig. 1J) and increasing intracellular NADPH levels (Fig. 1K), and effectively preventing FHdeficient UOK262 and FH-D238H Caki-2 cell death under glucose starvation (Figs. 1L and S1N).
局限
However, these cells also exhibit glucose dependency.；However, in FH-proficient cells, glucose deprivation leads to decreased NADPH levels, impaired NADPH-mediated GSH/thioredoxin antioxidant system function, and accumulation of reactive oxygen species (ROS)21,22.；However, the C264S mutation significantly reduced but did not fully eliminate dimers (with residual dimers detectable under long exposure).
对本项目的价值
中高价值：属「线粒体质量控制与氧化应激」方向；线粒体功能与氧化应激栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.3/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 95,721 字符，题名指纹 0.88，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：延胡索酸水合酶缺失在葡萄糖剥夺下触发双硫死亡
- 英文标题：Fumarate hydratase deficiency triggers disulfidptosis under glucose deprivation.
- 期刊与标识：Nature communications · PMID 42972140 · DOI 10.1038/s41467-026-78274-6 · PMC PMC13728156