Unknown

Dataset Information

0

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.

SUBMITTER: Jin L 

PROVIDER: S-EPMC4325424 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5372004 | BioStudies
2018-01-01 | S-EPMC5777230 | BioStudies
2019-01-01 | S-EPMC6359540 | BioStudies
2016-01-01 | S-EPMC5085137 | BioStudies
2020-01-01 | S-EPMC6957841 | BioStudies
1000-01-01 | S-EPMC5787800 | BioStudies
2020-01-01 | S-EPMC7465484 | BioStudies
2013-01-01 | S-EPMC3744468 | BioStudies
2017-01-01 | S-EPMC5368413 | BioStudies
2008-01-01 | S-EPMC2475696 | BioStudies