Journal: Nature Communications
Article Title: OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and increased succinate oxidation
doi: 10.1038/s41467-020-15237-5
Figure Lengend Snippet: a Relative GM-OXPHOS respiratory capacity with glutamate&malate (GM P /NS E ) in benign (blue) or malignant (red) samples carrying either no or only synonymous HPs (−) ( N BE = 36 and N CA = 23) versus samples carrying non-synonymous HPs (+) ( N BE = 14 and N CA = 27) in the coding regions of the mt-genome. Values present mean ± SD. Differences in mean values were tested for significance using Wilcoxon rank-sum test. b Comparison of relative GM-OXPHOS capacity in samples without mutations (−) ( N BE = 38 and N CA = 37) versus samples with mutations (+) ( N BE = 12 and N CA = 13) within the non-coding (control) region of the mt-genome. Values represent mean ± SD. c Impact of location of non-synonymous HPs on relative GM-OXPHOS capacities. Tumor tissue samples were categorized according to no HPs (−) (orange; N = 24), and HPs located in genes encoding proteins of CIII–CV (CO, ATP, CYB; green; N = 10) or in genes encoding proteins of CI (ND1–ND5; blue; N = 20). d – e Relative GM-OXPHOS (GM P /NS E , d ) and relative S-ET (S E /NS E , e ) respiratory capacities in malignant tissue samples harboring non-synonymous HPs in CI-coding mt-genes. Tumors were grouped into samples carrying no non-synonymous HPs ((−); N = 23), samples with variant levels of 30–60% (30–60%; N = 6) and samples with variant levels >60% (>60%; N = 4). Differences in mean values were tested for significance using one-way ANOVA followed by Tukey’s HSD test. f N-pathway (blue) and S-pathway (orange) respiratory capacities in malignant samples harboring high-level (>60%) non-synonymous HPs in either CIV-coding genes ( N = 4) or CI-coding genes ( N = 4). Differences of in mean values were tested for significance using Wilcoxon rank-sum test. Values presented in c-f represent mean values and individual data points. g S-pathway OXPHOS capacity upregulation by partial inhibition of N-pathway oxidative flux in benign (RWPE1, N = 3; EP156T, N = 3) and malignant (PC3, N = 6; LNCaP, N = 4; DuCaP, N = 3, N represents number of biologically independent experiments) prostate cell lines. Relative S-pathway OXPHOS capacity (normalized to total respiratory capacity, NS E ) with different degrees of N-pathway inhibition is shown for the five cell lines. Values represent mean ± SD. Source data are provided as a Source Data file.
Article Snippet: DuCaP prostate cancer cells were a gift from Dr. Schalken (Radboud University, Nijmegen, The Netherlands).
Techniques: Comparison, Control, Variant Assay, Inhibition
