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. 2023 Nov 20;6:1179. doi: 10.1038/s42003-023-05548-w

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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. 4 — a Heatmap of the top discriminant features between the IPD and control NESCs. b Circos plot showing the correlation between features contributing to the variation of the component 1. Correlation threshold: r = 0.9. c Correlation network of features contributing to the variation of the component 1. Correlation threshold: r = 0.95. d Relative abundance of glycerol-3-phosphate. Statistics: Welch’s t-test. Error bars represent mean + SD. N = 3 biologically independent samples. e Graphical representation of glycerol-3-phosphate (G3P) as an intermediate metabolite in glycolysis, lipid metabolism and oxidative phosphorylation and its role in NAD metabolism. G3P synthesis from dihydroxyacetone phosphate (DHAP) by cytosolic glycerol-3-phosphate dehydrogenase (cGPDH) regenerates cytosolic NAD+ from the NADH that is generated by glyceraldehyde-3-phosphate dehydrogenase in glycolysis. The G3P shuttle also facilitates electron transport between cytosol to mitochondria. Flavin linked mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) oxidases G3P at the same time reducing flavin adenine dinucleotide (FAD) to FADH₂ and transferring electrons to ubiquinone pool of the electron transport chain (ETC)_. ETC oxidazes NADH generated in TCA to replenish the mitochondrial NAD+ pool. G3P can also be produced from glycerol, which is the end product of lipolysis. f Intracellular ATP levels measured in relative light units (RLU) and normalized to the cell number in samples treated with vehicle, 20 nM quinolinic acid (QA) and 5 mM nicotinic acid (NA). Statistics: non-parametric Mann-Whitney test. Error bars represent mean + SD. N = 3 independent experiments.