Fig. 3: Iron scarcity impairs tricarboxylic acid (TCA) cycle activity at the iron-dependent enzymes ACO2 and SDH.
From: Iron deficiency causes aspartate-sensitive dysfunction in CD8+ T cells
CD8+ T cells were activated as described in Fig. 1a. For tracing experiments, T cells were activated in standard media for 24 h and then incubated in media containing 13C6-glucose or 13C5-glutamine for a further 24 h. a Relative metabolite abundance from T cells cultured in low iron (0.001 mg/mL holotransferrin) versus high iron (0.625 mg/mL holotransferrin), normalised to spiked in glutaric acid. Pooled relative total abundances from the 13C6-glucose and 13C5-glutamine experiments, n = 8. NEAA non-essential amino acids, EAA essential amino acids. P values are shown in red. b13C5-glutamine tracing, n = 4. Relative abundance of labelled and unlabelled metabolites calculated as the fraction labelled multiplied by the raw glutaric acid normalised abundance. Blue-filled circles indicate carbon atoms labelled from 13C5-glutamine. Empty circles indicate unlabelled carbon atoms. Relative abundance of c α-KG, d succinate, e fumarate and f malate mass isotopomers from 13C-glutamine tracing calculated as the fraction labelled multiplied by the raw glutaric acid normalised abundance, n = 4. g NAD+/NADH ratio. Data from independent experiments denoted by different symbols, n = 13. Data are mean ± SEM, where each datapoint per condition denotes cells from independent donor mice. Statistics are: a matched two-way ANOVA with the Geisser-Greenhouse correction and the Fisher’s least significant difference (LSD) test for multiple comparisons; b–f matched two-way ANOVAs with the Geisser-Greenhouse correction and the Sidak correction for multiple comparisons; g matched two-tailed t-test. Source data are provided as a Source Data file.
