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. 2022 Aug 5;13:4578. doi: 10.1038/s41467-022-32272-6

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© The Author(s) 2022

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 — NAD⁺/NADH ratio (a), NAD⁺ levels b and NADH levels (c) determined by NAD⁺/NADH-Glo bioluminescent Promega assay, n = 3 biological replicates (with three technical replicates each time), unpaired two-tailed t-tests, data are represented as mean ± SD. d Metabolic map and observed alterations of wt vs. cis cells, more elaborate results in Supplementary Fig. 6. e The use of α-ketobutyrate (αKB) by lactate dehydrogenase (LDH) to generate α-hydroxybutyrate (αHB) and NAD⁺. f 2 mM αKB supplementation of serine/glycine starved cis cells with 6 µM carboplatin treatment, n = 3 biological replicates (with three technical replicates each time), repeated measures two-way ANOVA, data are represented as mean ± SD, p = 0.0019. g NAD⁺/NADH ratio of αKB supplemented serine/glycine starved cis cells with carbo treatment, n = 3 biological replicates (with three technical replicates each time), unpaired two-tailed t-test, data are represented as mean ± SD, p = 0.0105. h Representative western blot of PHGDH in αKB supplemented carboplatin treated ser/gly starved cis cells, n = 3 biological replicates. i GI50 of wt and cis cells to the NAMPT inhibitor Daporinad determined with trypan blue counting, n = 4 biological replicates (with three technical replicates each), unpaired two-tailed t-test between GI50 values, data are represented as mean ± SEM, p = 0.0157. j Representative images of cis cells under 12 µM carboplatin and 0.4 nM Daporinad treatment and its combination, scale bar is 500 µm, n = 3 biological replicates (with three technical replicates each). Some schematic art pieces in d were used and modified from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/). Source data are provided as a Source Data file. Carbo carboplatin treated, αKB α-ketobutyrate, αHB α-hydroxybutyrate, LDH lactate dehydrogenase, ETC electron transport chain, TCA trycarboxylic acid cycle, PUFA polyunsaturated fatty acids, HUFA highly unsaturated fatty acids.