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. 2023 Mar 6;42(16):1294–1307. doi: 10.1038/s41388-023-02632-7

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© The Author(s) 2023

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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Fig. 5 — A Schematic pathway of L2HG and D2HG production (left) and the mRNA expression of ADHFE1, L2HGDH, OGDH, and DLST in paired non-neoplastic and CRC tissues (right). mRNA levels were measured using microarray analysis. B Representative chromatograms (left) and levels (right) of L2HG in HT29 cells transfected with OGDH and/or L2HGDH siRNA. Data represent the mean ± SD of three independent experiments. C ATF4 protein expression in the whole and nuclear fractions of OGDH and L2HGDH knockdown HT29 cells. D Effect of OGDH and L2HGDH knockdown on the mRNA expression of ATF4 target genes in HT29 cells. mRNA levels were measured using real-time PCR. Data are the average of three technical replicates and are representative of at least two independent experiments with similar results. E S6K phosphorylation in OGDH and L2HGDH knockdown HT29 cells. F Effect of Torin1 (250 nM) on the expression of nuclear ATF4 in OGDH and L2HGDH knockdown HT29 cells.