Figure 3.

Fibroblast proteomic analysis of the proband with the NAXD c.441+3A>G variant. (A) Volcano plot showing protein abundances of mitochondrial proteins (based on MitoCarta3.0 annotations) detected through quantitative proteomics in the fibroblasts from all five NAXD cases relative to healthy controls (n = 5). Horizontal line represents p = 0.05 and the vertical lines represent fold changes of ± 1.5. Blue = OXPHOS subunits. (B) Relative complex abundance (RCA) profiles from quantitative proteomics revealed a significant reduction in mitochondrial OXPHOS complex subunits (CI and CV) and mitoribosomal proteins (large subunit ‘LSU’ and small subunit ‘SSU’) in fibroblasts from the adult onset NAXD case against controls (n = 5). Individual protein subunits are represented by a single dot. Overall mean values of subunits within each complex, which have been normalised to mitochondrial content levels, are represented by the middle bar. Upper and lower bars represent 95% confidence intervals. The mean ratio of each complex is shown as a percentage value on the top of each group. ns; p > 0.05, **; p ≤ 0.01, ****; p ≤ 0.0001. (C) Gene ontology (GO) terms for top ten biological processes enriched in cellular proteins decreased in abundance (p < 0.05, fold change −1.5) within three or more NAXD cases analysed by quantitative proteomics. Biological processes were determined by Enrichr [7,8] and ranked by adjusted p-value. The combined score, determined by multiplying the p-value and z-scores, is shown on the X-axis (full list in Supplementary Table S2).