Fig. 3: Multi-omics reveal perinatal mitochondrial stress, cysteine deficiency, and metabolic maturation defect.

a Proteomic volcano plots of top enriched pathways from P1 proteomic analysis, Polg^MutTwOE vs WT (n = 6 + 5); areas above the Q < 0.01 significance threshold shaded according to positive (red) or negative (blue) log₂ fold-change. b Enriched KEGG pathways in proteomic hits, fold enrichment, and log₁₀ p-value in lollipop plot (FDR-corrected hypergeometric p-values, see methods). c MitoCarta3.0 classification of detected proteins based on mitochondrial localization, P1. d Respiratory chain subunits change from P1 proteomics, by respiratory complex (I-IV). e Metabolomics volcano plot of Polg^MutTwOE vs WT (n = 7 + 6), P1. FDR-adjusted two-tailed t-test p < 0.01 significance threshold shaded as in (a). f Simplified cysteine metabolic pathway summarizing the direction of significant changes in P1 metabolomics by color. g Heatmap of log₂ fold-change of significantly affected metabolites across all measured genotypes. P values from t-test vs WT (n = 6): (p < 0.05*, 0.01**, 0.001***). h Transcriptomics volcano plot of Polg^MutTwOE vs WT (n = 4 + 4), E16.5; p < 0.01 threshold shaded as in (a), significantly changed hits categorized into key pathways. i Enriched KEGG pathways in the transcriptomic hits, log₁₀ p-value in lollipop plot (as in b). j Representative examples of ISR^mt gene expression landscapes across genotypes, bar plots represent mean ± SEM. See methods for details on each p-value derivation from the omic analyzes. 1C = one-carbon, Mito = Mitochondrial protein, OXPHOS = oxidative phosphorylation machinery, NS = not significantly changed, ECM = extracellular matrix, ISR^mt = mitochondrial integrated stress response.