Fig. 4
Analysis of the proteome of POLG1Q811R variant and healthy control MDNS reveals alterations in several pathways linked to PD pathology. a Protein expression variances between POLG1 variant and healthy control MDNS as principal component analysis (PCA). The first two axes (PCA axis 1 and 2) of the PCA explain 51% of the variance. Red and turquoise dots represent healthy control and POLG1 variant clones/differentiations, respectively. b Volcano plot displaying differentially expressed proteins in POLG1 variant and healthy control MDNS. Y-axis corresponds to the log10 (p-value), and X-axis displays the log2 (fold change) values. The cut-off for significantly altered protein levels is set at P < 0.001. The red dots represent significantly down-regulated proteins, and the green dots represent significantly up-regulated proteins. c Heat map representing color-coded expression levels (red for down-regulated and green for up-regulated) of proteins differentially expressed between POLG1 variant (cyan) and healthy control (orange) MDNS, with P < 0.001. d Abundance levels for neuronal markers TUBB3 and TH and mitochondrial markers TOMM20 and VDAC1 in POLG1 variant and healthy control MDNS identified by LC MS/MS quantitative proteomics. e and f Western blot confirming no difference in the levels of TH, TOMM20 and VDAC1 between POLG1 variant and healthy control MDNS. Protein expression levels are normalized to b-ACTIN. Results are presented as ± SEM, n = 4 independent experiments. g Ingenuity Pathways analysis (IPA) identifying regulated pathways for differently expressed proteins POLG1 variant and healthy control MDNS. The figure shows the altered canonical pathways in IPA canonical pathways analysis. The Y-axis shows the regulated pathways and the X-axis shows the –log(p-value). A cut-off of P = 0.001 was used for the proteins to be included in the analyses. h Top diseases and functions identified based on the differentially expressed proteins, with indication of scores and focus molecules for each category