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. 2019 Oct 30;9:15665. doi: 10.1038/s41598-019-52169-7

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Schematic overview of the potential mechanisms of UGCG induced cellular processes. (A) UGCG overexpression leads to an increased intracellular glutamine concentration that fuels (1) glutathione synthesis via glutamate processing (green arrow = elevated mRNA level in MCF-7/UGCG OE cells as compared to MCF-7/empty cells; * = no difference; red arrow = decreased mRNA level in MCF-7/UGCG OE cells as compared to MCF-7/empty cells) (B) (2) TCA cycle turnover (green arrow = elevated metabolites analyzed by ¹³C₅-glutamine labelling assay in MCF-7/UGCG OE cells as compared to MCF-7/empty cells) and (3) enhanced amino acid synthesis. EAAs = essential amino acids, GEM = glycosphingolipid-enriched microdomain, xCt = glutamate/cysteine antiporter, ASCT2 = alanine-serine-cysteine transporter 2, Lat1 = L-type amino acid transporter 1, GLS/GLS2 = glutaminase/glutaminase 2, GCLC = glutamate-cysteine-ligase, GSS = glutathione synthase, GSH = glutathione, GSSG = glutathione disulfide, GSR = glutathione reductase, NFE2L2 = Nuclear factor (erythroid-derived 2)-like 2, Aralar = mitochondrial aspartate-glutamate-carrier, GluR1 = glutamate carrier, GLUD = glutamate dehydrogenase.