Glutamate Dehydrogenase 1 Signals through Antioxidant Glutathione Peroxidase 1 to Regulate Redox Homeostasis and Tumor Growth
Copyright policy )Glutamate Dehydrogenase 1 Signals through Antioxidant Glutathione Peroxidase 1 to Regulate Redox Homeostasis and Tumor Growth
How mitochondrial glutaminolysis contributes to redox homeostasis in cancer cells remains unclear. Here we report that the mitochondrial enzyme glutamate dehydrogenase 1 (GDH1) is commonly upregulated in human cancers. GDH1 is important for redox homeostasis in cancer cells by controlling the intracellular levels of its product alpha-ketoglutarate and subsequent metabolite fumarate. Mechanistically, fumarate binds to and activates a reactive oxygen species scavenging enzyme glutathione peroxidase 1. Targeting GDH1 by shRNA or a small molecule inhibitor R162 resulted in imbalanced redox homeostasis, leading to attenuated cancer cell proliferation and tumor growth.
- University of Chicago United States
- Emory Healthcare United States
- Yale University United States
- Winship Cancer Institute United States
- The University of Texas Southwestern Medical Center United States
Cancer Research, Glutathione Peroxidase, Leukemia, Carcinogenesis, Primary Cell Culture, Cell Biology, Glutathione, Antioxidants, Mitochondria, Gene Expression Regulation, Neoplastic, Glutathione Peroxidase GPX1, Oncology, Fumarates, Glutamate Dehydrogenase, Humans, Ketoglutaric Acids, Reactive Oxygen Species, Oxidation-Reduction, Signal Transduction
Cancer Research, Glutathione Peroxidase, Leukemia, Carcinogenesis, Primary Cell Culture, Cell Biology, Glutathione, Antioxidants, Mitochondria, Gene Expression Regulation, Neoplastic, Glutathione Peroxidase GPX1, Oncology, Fumarates, Glutamate Dehydrogenase, Humans, Ketoglutaric Acids, Reactive Oxygen Species, Oxidation-Reduction, Signal Transduction
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