The glutamate/cystine xCT antiporter antagonizes glutamine metabolism and reduces nutrient flexibility
Citations Over TimeTop 1% of 2017 papers
Abstract
As noted by Warburg, many cancer cells depend on the consumption of glucose. We performed a genetic screen to identify factors responsible for glucose addiction and recovered the two subunits of the xCT antiporter (system xc-), which plays an antioxidant role by exporting glutamate for cystine. Disruption of the xCT antiporter greatly improves cell viability after glucose withdrawal, because conservation of glutamate enables cells to maintain mitochondrial respiration. In some breast cancer cells, xCT antiporter expression is upregulated through the antioxidant transcription factor Nrf2 and contributes to their requirement for glucose as a carbon source. In cells carrying patient-derived mitochondrial DNA mutations, the xCT antiporter is upregulated and its inhibition improves mitochondrial function and cell viability. Therefore, although upregulation of the xCT antiporter promotes antioxidant defence, it antagonizes glutamine metabolism and restricts nutrient flexibility. In cells with mitochondrial dysfunction, the potential utility of xCT antiporter inhibition should be further tested.
Related Papers
- → The mystery of the human proton-organic cation antiporter: One transport protein or many?(2022)31 cited
- → Identification and Characterization of Functional Residues in a Na+/H+ Antiporter (NhaA) from Escherichia coli by Random Mutagenesis(1997)46 cited
- → Regulation of the mitochondrial Na+Ca2+ antiport by matrix pH(1991)54 cited
- → Isolation and properties of a mutant of Escherichia coli possessing defective Na+/H+ antiporter.(1987)38 cited
- Na~+/H~+Antiporter and Its Relationship with Plant Salt Tolerance(2006)