Fig. 7
Functional changes in glycolysis but not in the oxidative phosphorylation of POLG1 p.Q811R variant cultures support protein alteration identified by quantitative proteomic analysis. a Oxygen consumption rates (OCRs) of 100 DIV dissociated POLG1 variant and healthy control cultures, normalized to protein content, illustrating levels of basal respiration, ATP-coupled (oligomycin-sensitive) respiration, ATP-uncoupled respiration after FCCP treatment, spare respiratory capacity, as well as contribution of mitochondrial complex I- and complex II-linked respiration calculated from the effect of treatment with NV118, a cell-permeable prodrug of the complex II substrate succinate. Results are presented as ± SEM, n = 4 independent experiments; unpaired t-test. b Abundance levels for LDHA and PFKM in POLG1 variant and healthy control MDNS identified by LC MS/MS quantitative proteomics. c Western blot analysis shows significant upregulation of PFKM and a trend for increase of LDHA in POLGQ811R MDNS compared to healthy control MDNS. Protein levels are normalized to b-ACTIN. Results are presented as ± SEM; n = 4 independent experiments; *** indicates P < 0.001; unpaired t-test. d Extracellular acidification rates (ECARs) of 100 DIV dissociated POLG1 variant and healthy control cultures, normalized to protein content, illustrating levels of basal glycolysis and glycolytic reserve following treatment with oligomycin. Results are presented as ± SEM n = 4 independent experiments. * indicates P < 0.05; unpaired t-test