Extended Data Fig. 3: Expression of the yeast NDI1 protein in lung epithelial cells does not disrupt lung development or physiology, and restores abnormal alveolar structures in NDUFS2 cKO mice.
From: Mitochondrial integrated stress response controls lung epithelial cell fate
a, Representative images of lung histology (hematoxylin-eosin stain) from 48-day-old mice. NDI1LSL mice and SFTPC-Cre;NDI1LSL mice are referred to as WT and NDI1, respectively (scale bar, 50 μm). b, Box plots of static lung compliance in 48–49-day-old mice (WT n = 12; NDI1 n = 10 mice with technical replicates), p = 0.6744 by Mann-Whitney test. c, Intracellular NADH/NAD+ ratios from metabolomics analysis of lung epithelial cells isolated from 35-day-old mice (NDUFS2 control n = 8; NDUFS2 control/NDI1 n = 7; NDUFS2 cKO n = 7; NDUFS2 cKO/NDI1 n = 8 mice). p = 0.0006 by Kruskal-Wallis test. d, The frequency distribution of alveolar thickness measured in hematoxylin-eosin stained lung histology of 46–49-day-old mice (n = 4 mice, two males and two females per genotype). 4–6 randomly selected fields of view from each mouse were evaluated. The x axis shows alveolar thickness bins, and the y axis shows the number of alveolar pixels that belong to the respective alveolar thickness bin normalized to the total alveolar pixel count in the image. Each animal is represented by its own color. Statistical significance for genotype was calculated based on F-test for a linear model (p = 4.66 x 10−5). e, Representative images of lung histology (hematoxylin-eosin stain) from 2-year-old mice (scale bar, 50 μm), f, Box plots of lung compliance in 18–25-month-old mice (NDUFS2 control n = 4; NDUFS2 control/NDI1 n = 5; NDUFS2 cKO/NDI1 n = 15 mice with technical replicates), p = 0.3847 by Kruskal-Wallis test. g–h, Metabolomics analysis of lung epithelial cells isolated from 35-day-old mice (NDUFS2 control n = 8; NDUFS2 control/NDI1 n = 7; NDUFS2 cKO n = 7; NDUFS2 cKO/NDI1 n = 8 mice). Lines represent median. Relative abundance of aspartate. p = 0.7515 by Kruskal-Wallis test (g). Relative abundance of asparagine. p = 0.0253 by Kruskal-Wallis test. * p = 0.0259 by Dunn’s multiple comparisons test (h).
