Figure 7. Mitochondrial OXPHOS dysfunction causes upregulation of de novo serine synthesis in normal ageing human colonic crypts.

Immunoflourescent images showing co-labelling of OXPHOS proteins and SSP enzymes in normal human colonic epithelium. Scale bars; 50µm. Immunofluorescence was performed for each antibody on n=12 human samples. Representative images are shown. b-d: Quantification of the levels of PHGDH, PSAT1 and MTHFD2 in individual human crypts. Every OXPHOS deficient crypt on the section was quantified and OXPHOS normal crypts on the same section were randomly sampled. In b the number of crypts analysed from left to right is: n=45, 46, 40, 62, 43, 50, 28, 29, 21, 16, 16, 17, 33, 31, 41, 17, 20, 8, 32, 27, 15, 17, 24, 24. In c the number of crypts analysed from left to right is: n=47, 57, 58, 70, 44, 56, 54, 39, 73, 11, 21, 20, 33, 33, 39, 16, 30, 8, 61, 45, 31, 22, 51, 49. In d the number of crypts analysed from left to right is: 23, 67, 40, 61, 44, 47, 42, 32, 108, 15, 37, 38, 59, 60, 58, 26, 62, 10, 48, 40, 31, 24, 60, 59. Error bars show mean ±s.d. Data were analysed by two-sided linear mixed effect regression model with mouse ID as a random effect, p<0.0001 in all comparisons. e: Schematic showing the hypothesised mechanism by which mtDNA mutations and OXPHOS defects contribute to tumorigenesis. ***p<0.001