Figure 1.

Immunometabolic response to P. aeruginosa. LPS activates the infected macrophage, stimulating glycolysis and downregulating oxidative phosphorylation (OXPHOS). This promotes glutamine-dependent anaplerosis, which replenishes succinate for oxidation to fumarate by mitochondrial succinate dehydrogenase (SDH). The resulting increase in mitochondrial transmembrane potential (∆Ψ) and over-reduction of the ubiquinone pool reverse electron flow to complex I, where they escape as reactive oxygen species (ROS). Both ROS and succinate stabilize HIF-1α, which translocates to the nucleus and binds to its target promoter regions, increasing Il-1β transcription. The succinate-driven inflammation is regulated by the production of the anti-inflammatory metabolite itaconate.