Cell Metab. 30, 352–363 (2019)

It is becoming increasing clear that cellular metabolism via glycolysis and oxidative phosphorylation greatly affects the functionality of activated immune cells. In Cell Metabolism, Puleston et al. show that hypusination, a polyamine-dependent post-translational modification, of the translation factor eIF5A boosts mitochondrial respiration by enhancing the translation of mitochondrial enzymes that catalyze multiple steps of the tricarboxylic acid cycle. Inhibition of the hypusine–eIF5A axis diminishes oxidative phosphorylation and the abundance of metabolites of the tricarboxylic acid cycle. In contrast, glycolytic enzymes are not as sensitive to hypusination of eIF5A. Hypusination of eIF5A is upregulated in macrophages stimulated with the cytokine IL-4 but not in those stimulated with the cytokine IFN-γ. In vivo modulation of eIF5A hypusination reduces macrophage-dependent control of the parasite Heligmosomoides polygyrus but does not alter responses to the injection of lipopolysaccharide, which shows that this modification influences macrophage function.