Fig. 2

Colonic mitochondriopathy with a robust gene signature for reduced rectal mitochondrial energy functions in UC. a Thirteen mitochondrial-encoded genes are downregulated in UC vs. control with their fold change, FDR corrected P value, and associated mitochondrial complex as indicated. High-Resolution Respirometry was performed on fresh colon biopsies (5 control, 9 with active UC, and 9 with inactive UC) using the Oroboros O2k modular system to evaluate the activity of Complex I (b) and Complex II (c) of the electron transport chain. JC1 staining and FACS analysis were used to define the mitochondrial membrane potential of d EpCAM + epithelial cells and e CD45 + leukocytes isolated from colon biopsies (7 controls, 6 active UC, and 7 with inactive UC, 85–99% viability). Colon PPARGC1A (PGC-1α) expression for f PROTECT cohort, h RISK cohort in (transcripts per million (TPM) values), and for j adult UC cohort (GSE59071¹²) in normalized values was plotted after stratifying the samples as indicated. g, i, k Krebs cycle TCA gene signature PCA PC1 for the above cohorts is plotted, samples are stratified as indicated. l Representative rectal MT-CO1 and COX5A immunohistochemistry (complex IV) for Ctl (n = 14), inactive (n = 10), and active UC (n = 11) with moderate Mayo endoscopic subscore and moderate PUCAI. Scale bar represents 50 μm. m Frequency of MT-CO1-positive and COX5A-positive epithelial cells out of the total epithelial cells for controls, inactive UC, and active UC. Lines in the scatter dot plots represent mean and SEM. Kruskal−Wallis with Dunn’s Multiple Comparison or ANOVA with false discovery rate (FDR) was used. *All two-sided P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. UC ulcerative colitis, L2 cCD colon-only Crohn’s disease L3 iCD ileo-colonic Crohn’s disease