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. 2024 Jun 15;15:5115. doi: 10.1038/s41467-024-49298-7

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© The Author(s) 2024

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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Fig. 4 — A–B The synthetic lethality between ACSL3 and NF2 is rescued by treating cells with a lipid mix (1%) (A) but not by the antioxidant n-acetylcysteine (NAC, 1 mM) (B). Relative cell number (CellTiter-Glo) normalized to the control sgRNA for each condition. Bars = mean ± SD. Significance by two-way ANOVA and Tukey’s multiple comparisons test. n = 4 (A) or 3 (B) biological replicates. C Synthetic lethality of NF2 and ACSL3 is rescued by Liproxstatin. Relative cell number (CellTiter-Glo) upon treatment with the ferroptosis inhibitor Liproxstatin. Values are normalized to control sgRNA. Bars = mean ± SD. Statistical analysis shown is a two-way ANOVA and Tukey’s multiple comparisons test; n = 5 biological replicates. D NF2 knockout Schwann cells have mildly elevated lipid peroxidation levels, assessed using BODIPY 581/591 C11 and flow cytometry. Ratio of oxidized/reduced lipids were normalized to untreated NF2-WT background levels. Erastin treatment (10μM-5hrs) was used as a positive control for lipid peroxidation. Bars = mean ± SD. Significance by two-way ANOVA and Tukey’s multiple comparisons test. n = 3 biological replicates. E–G The synthetic lethality between NF2 and G6PD is rescued by (G) the antioxidant n-acetylcysteine (NAC, 1 mM), but not by (E) Liproxstatin (1 μM), or by (F) supplementation with 1% Lipid Mix. Relative cell numbers, normalized to the DMSO control treatment condition, assayed by CellTiter-Glo. G6PDi-1 used at 25 µM. Bars = means ± SD. Significance by two-way ANOVA and Tukey’s multiple comparisons test. n = 3 biological replicates. H G6PDi-1 induces cell death (assayed by CellTox) in NF2-KO Schwann cells, and is rescued by NAC. Cell death values are normalized to cell number (CellTiter-Glo). Bars = mean ± SD. Significance by two-way ANOVA and Tukey’s multiple comparisons test. n = 5 independent experiments each with biological quadruplicates. Source data are provided as a Source Data file.