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. 2020 Feb 4;11:698. doi: 10.1038/s41467-020-14433-7

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Fig. 8 — Macrophage activation in the presence of Nitric Oxide (NO) results in multiple metabolic rewirings. Aconitase 2 is inhibited and entrance of carbon into TCA cycle via pyruvate dehydrogenase is halted. In turn, compensatory carboxylation and glutaminolysis are enhanced, leading to citrate accumulation and limited itaconate. Because of the breaks, the lack of NADH and reduced substrates leads to inactive mitochondrial complexes. In Nos2^−/− BMDMs glycolytic flux is maintained and carbon passage through PDH and ACO2 is intact. In this scenario, production of itaconate is increased and mitochondrial complexes display full functional activity. The arrows represent the general direction of the metabolic flow in the system with the specific contribution of glucose (purple) and glutamine (green). PDH pyruvate dehydrogenase, ACO2 mitochondrial aconitase, IDH isocitrate dehydrogenase, LPS lipopolysaccharide, IFNγ interferon γ.