Fig. 3: Tricarboxylic acid (TCA) cycle remodelling in m.5019 A>G macrophages. | Nature Communications

Fig. 3: Tricarboxylic acid (TCA) cycle remodelling in m.5019 A>G macrophages.

From: An inherited mitochondrial DNA mutation remodels inflammatory cytokine responses in macrophages and in vivo in mice

Fig. 3

a Heatmap comparing metabolite levels in non-stimulated (non-stim) (α-KG, P = 0.001812; Fumarate, P = 0.006172; Malate, P = 0.000451) and lipopolysaccharide (LPS)-stimulated (α-KG, P = 0.005704; Succinyl-CoA, P = 0.025485; Aspartate, P = 0.047568) wildtype (WT) and m.5019A>G BMDMs (n = 5; LPS 6 h; left), and comparing metabolite levels in non-stim WT and m.5019A>G BMDMs in the presence or absence of glutamine (Gln) (n = 3; LPS 4 h; right) (Citrate, P = 0.008855; Isocitrate, P = 0.000054; α-KG, P = 0.0000001; Succinate, P = 0.0128505; Fumarate, P = 0.0000541; Malate, P = 0.0000116; Aspartate, P = 0.0297496). b α-Ketoglutarate (α-KG)/succinyl-CoA and α-KG/succinate ratio in non-stim WT and m.5019A>G BMDMs (n = 5). c Oxoglutarate dehydrogenase complex (OGDHC) and pyruvate dehydrogenase complex (PDHC) E3 subunit (DLD) levels from proteomics in non-stim WT (n = 4), non-stim m.5019A>G (n = 5), LPS-stimulated WT (n = 6; 6 h) and LPS-stimulated m.5019A>G BMDMs (n = 7; 6 h) (P = 0.000047). d Schematic of U-13C-glutamine tracing into the tricarboxylic acid (TCA) cycle, indicating oxidative versus reductive labelling patterns. e m + 5 labelling from U-13C-glutamine in isocitrate and citrate in non-stim and LPS-stimulated WT and m.5019A>G BMDMs (n = 5; LPS 6 h). f m + 5 labelling in L-2-hydroxyglutarate (L-2-HG) from U-13C-glutamine in non-stim and LPS-stimulated WT and m.5019A>G BMDMs (n = 3; LPS 6 h). g Schematic of U-13C-glucose tracing into the TCA cycle, indicating oxidative versus reductive labelling patterns. h m + 3 labelling from U-13C-glucose in citrate, malate (P = 0.000405; P = 0.000405) and succinate in non-stim and LPS-stimulated WT and m.5019A>G BMDMs (n = 5; LPS 24 h). Data are mean or mean ± s.e.m. n number represents independent biological replicates (mice) from a minimum of three independent experiments. P-values calculated using two-tailed Student’s t test for two group comparisons or multiple two-tailed unpaired t tests corrected for multiple comparisons using Benjamini, Krieger and Yekutieli method. *** P < 0.001 ** P < 0.01 * P < 0.05.

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