异柠檬酸脱氢酶
磷酸戊糖途径
谷氨酰胺
苹果酸酶
谷氨酰胺分解
癌细胞
生物化学
IDH1
生物
胞浆
瓦博格效应
葡萄糖摄取
细胞生物学
糖酵解
新陈代谢
癌症
内分泌学
酶
脱氢酶
氨基酸
胰岛素
突变
基因
遗传学
作者
Minfeng Ying,Duo You,Xiao-liang Zhu,Limeng Cai,Sha Zeng,Xun Hu
出处
期刊:Redox biology
[Elsevier]
日期:2021-10-01
卷期号:46: 102065-102065
被引量:64
标识
DOI:10.1016/j.redox.2021.102065
摘要
Although glucose, through pentose phosphate pathway (PPP), is the main source to generate NADPH, solid tumors are often deprived of glucose, hence alternative metabolic pathways to maintain NADPH homeostasis in cancer cells are required. Here, we report that lactate and glutamine support NADPH production via isocitrate dehydrogenase 1 (IDH1) and malic enzyme 1 (ME1), respectively, under glucose-deprived conditions. Isotopic tracing demonstrates that lactate participates in the formation of isocitrate. Malate derived from glutamine in mitochondria shuttles to cytosol to produce NADPH. In cells cultured in the absence of glucose, knockout of IDH1 and ME1 decreases NADPH/NADP+ and GSH/GSSG, increases ROS level and facilitates cell necrosis. In 4T1 murine breast tumors, knockout of ME1 retards tumor growth in vivo, with combined ME1/IDH1 knockout more strongly suppressing tumor growth. Our findings reveal two alternative NADPH-producing pathways that cancer cells use to resist glucose starvation, reflecting the metabolic plasticity and flexibility of cancer cells adapting to nutrition stress.
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