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. 2023 Mar 15;615(7953):712–719. doi: 10.1038/s41586-023-05793-3

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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 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 — Data are mean ± s.e.m. (n = 3 biological replicates), unpaired two-tailed t-test unless specified otherwise. a, 3D reconstruction of LDs (green), mitochondria (red) and nucleus (blue) in an OXPHOS^HI LUAD cell and an OXPHOS^LO LUSC cell. Zoomed-in images (lower panels) are of the regions outlined in white from the 3D reconstructed cells (upper panels). The lower left panel is a side view of the interaction between mitochondria and LDs. The lower right panel comprises a front and back view of LDs in close proximity to but not contacting mitochondria. Scale bars, 3 μm. b, Quantification of the total volume and number of LDs in 3D-rendered LUAD and LUSC cells imaged by SBEM (n > 150 LDs). c, Percentage of spatially compartmentalized mitochondria in OXPHOS^HI LUAD cells (n = 3 biological replicates, n > 1,200 mitochondria) and OXPHOS^LO LUSC cells (n = 3 biological replicates, n > 750 mitochondria). d, Co-staining of oil red O and haematoxylin in OXPHOS^HI LUAD (H1975) and OXPHOS^LO LUSC (RH2) human xenografts. Scale bars, 40 μm. e,f, Ratio of area between oil red O and haematoxylin staining for OXPHOS^HI LUAD and OXPHOS^LO LUSC xenografts (e, n = 5 LUAD tumours, n = 5 LUSC tumours) and GEMMs (f, n = 6 LUAD tumours, n = 7 LUSC tumours). g, Co-staining of MTDR (purple), BODIPY (green) and Hoechst (blue) in H1975 and RH2 cells. Scale bars, 3 μm. h,i, Average number of LDs and PDM in human LUAD and SCC cells (n > 300 cells per cell line). j, 2D SBEM image (left) and 3D reconstruction (right) of PDM and associated crista structure of an OXPHOS^HI LUAD cell. Scale bar, 500 nm. k, Percentage of type I, II and III cristae in PDM population (n > 400 mitochondria). One-way ANOVA, Dunnett test. l, Percentage of change in basal OCR of human LUAD and SCC cells in response to UK5099, etomoxir and BPTES. m, Cell count of H1975 and RH2 cells proliferating under the conditions of normal medium (25 mM glucose), and medium with no free fatty acids (FFAs), low glucose (12 mM) or no glutamine.

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