Non-canonical glutamine transamination sustains efferocytosis by coupling redox buffering to oxidative phosphorylation.

ABSTRACT: Macrophages rely on tightly integrated metabolic rewiring to clear dying neighboring cells by efferocytosis during homeostasis and disease. Here we reveal that glutaminase-1-mediated glutaminolysis is critical to promote apoptotic cell clearance by macrophages during homeostasis in mice. In addition, impaired macrophage glutaminolysis exacerbates atherosclerosis, a condition during which, efficient apoptotic cell debris clearance is critical to limit disease progression. Glutaminase-1 expression strongly correlates with atherosclerotic plaque necrosis in patients with cardiovascular diseases. High-throughput transcriptional and metabolic profiling reveals that macrophage efferocytic capacity relies on a non-canonical transaminase pathway, independent from the traditional requirement of glu

SUBMITTER: Merlin J 

PROVIDER: S-EPMC7611882 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature