Fig. 2: Itaconate is a substrate for mitochondrial metabolism in mouse liver and kidney.
From: In vivo itaconate tracing reveals degradation pathway and turnover kinetics
a, Plasma itaconate levels in response to itaconate treatment with elimination half-time (T1/2). b, Plasma succinate levels in response to itaconate treatment. c, Levels of TCA cycle intermediates after itaconate treatment for indicated times. d, Itaconate levels in urine. e, Labelling (1 − M0) on TCA cycle intermediates in plasma from [U-13C5]itaconate. f, Levels of itaconate in different tissues. g, Ratio of succinate (nmol mg−1 protein) over fumarate (nmol mg−1 protein) after itaconate treatment in different tissues. h, Label (1 − M0) on citrate from [U-13C5]itaconate in different tissues. i, M2 labelling on citrate from [U-13C5]itaconate in different tissues. j, Schematic depicting itaconate clearance pathway and SDH inhibition. Stashed arrows depict indirect metabolic pathways. Mice were injected with 400 mg kg−1 body weight [U-13C5]itaconate. Data are presented as means; error bars, s.e.m. Plasma samples at 0 min (n = 4), 15 min (n = 9), 30 min (n = 4) and 45 min (n = 4); tissue samples at 0 min (n = 4), 15 min (n = 5) and 45 min (n = 4); urine samples at 0 min (n = 3), 15 min (n = 4) and 45 min (n = 3). P values were calculated by one-way ANOVA compared to 0 min itaconate with Fisher’s LSD post hoc test (a,b,d) or two-way ANOVA (c,e–h); *P < 0.05; **P < 0.01, ***P < 0.001, #P < 0.0001. Exact P values are indicated in each figure panel.
