@article{0479a1e68fca4962b061bf346d645b46,
title = "Glutamate Dehydrogenase 1 Signals through Antioxidant Glutathione Peroxidase 1 to Regulate Redox Homeostasis and Tumor Growth",
abstract = "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.",
author = "Lingtao Jin and Dan Li and Alesi, {Gina N.} and Jun Fan and Kang, {Hee Bum} and Zhou Lu and Boggon, {Titus J.} and Peng Jin and Hong Yi and Wright, {Elizabeth R.} and Duc Duong and Seyfried, {Nicholas T.} and Robert Egnatchik and DeBerardinis, {Ralph J.} and Magliocca, {Kelly R.} and Chuan He and Arellano, {Martha L.} and Khoury, {J. Hanna J} and Shin, {Dong M.} and Khuri, {Fadlo R.} and Sumin Kang",
note = "Funding Information: We acknowledge Dr. Anthea Hammond for editorial assistance. We thank the Integrated Cellular Imaging Core of Emory University. This work was supported in part by NIH grants R01 CA175316 (S.K.), F31 CA183365 (G.A.), and S10 RR025679 01 (P.S.), ACS grant RSG-11-081-01 (S.K.), Georgia Cancer Coalition (H.J.K.), and the Hematology Tissue Bank of the Emory University School of Medicine. G.A. is an NIH predoctoral fellow. H.J.K., F.R.K., and S.K. are Georgia Cancer Coalition Scholars. S.K. is a Robbins Scholar and an American Cancer Society Basic Research Scholar. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = feb,
day = "9",
doi = "10.1016/j.ccell.2014.12.006",
language = "English (US)",
volume = "27",
pages = "257--270",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}