Macrophage metabolic adaptation to heme detoxification involves CO-dependent activation of the pentose phosphate pathway.

ABSTRACT: Heme is an essential cofactor for numerous cellular functions, but release of free heme during hemolysis results in oxidative tissue damage, vascular dysfunction, and inflammation. Macrophages play a key protective role in heme clearance; however, the mechanisms that regulate metabolic adaptations that are required for effective heme degradation remain unclear. Here we demonstrate that heme loading drives a unique bioenergetic switch in macrophages, which involves a metabolic shift from oxidative phosphorylation toward glucose consumption. Metabolomic and transcriptional analysis of heme-loaded macrophages revealed that glucose is funneled into the pentose phosphate pathway (PPP), which is indispensable for efficient heme detoxification and is required to maintain redox homeostasis. We dem

SUBMITTER: Bories GFP 

PROVIDER: S-EPMC7515686 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature