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. 2021 Sep 23;11:18910. doi: 10.1038/s41598-021-98082-w

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© The Author(s) 2021

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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2-Oxyglutarate prevents IMS32 cell death, mitochondrial dysfunction and ATP depletion under high-glucose pyruvate-starved conditions. (A) Cell viability at 24 h in the [Glc 5 mM/Pyr (+)] (blue), [Glc 5 mM/Pyr (−)] (yellow), [Glc 15 mM/Pyr (+)] (brown), [Glc 15 mM/Pyr (−)] (green), and [Glc 15 mM/Pyr (−)] supplemented with TCA cycle intermediates (red) groups was determined by MTS assay. (B) Time course of OCR in the [Glc 5 mM/Pyr (+)] (blue), [Glc 5 mM/Pyr (−)] (yellow), [Glc 100 mM/Pyr (+)] (brown), [Glc 100 mM/Pyr (−)] (green), and [Glc 100 mM/Pyr (−)/2-OG (+)] (red) groups measured by Extracellular Flux Analyzer and Cell MitoStress Test. (C) Mitochondrial ATP production under these five conditions was estimated by changes in OCR through sequential addition of oligomycin and FCCP. Values represent mean + SD from six (A) and 9–10 (B and C) experiments (individual values are depicted as circles, triangles, pluses, crosses and asterisks). (A and C) * P < 0.05, ** P < 0.01. (B) [Glc 100 mM/ Pyr (−)] compared with (a) all the other groups (P < 0.01), (b) [Glc 5 mM/Pyr (+)], [Glc 100 mM/ Pyr (+)], or [Glc 100 mM/Pyr (−)/2-OG (+)] (P < 0.01), (c) [Glc 100 mM/Pyr (−)/2-OG (+)] (P < 0.01) or [Glc 100 mM/ Pyr (+)] (P < 0.05), (d) [Glc 100 mM/Pyr (−)/2-OG (+)] (P < 0.01), and (e) [Glc 100 mM/ Pyr (+)] or [Glc 100 mM/Pyr (−)/2-OG (+)] (P < 0.01). Ac CoA, acetyl CoA; Cit, citrate; ISC, isocitrate; 2-OG, 2-oxyglutarate; Suc CoA, succinyl CoA; Suc, succinate; Fum, fumarate; Mai, malate; and OAA; oxaloacetate.