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

מאת: Merlin J., Ivanov S., Dumont A., Sergushichev A., Gall J., Stunault M., Ayrault M., Vaillant N., Castiglione A., Swain A., Orange F., Gallerand A., Berton T., Martin J.-C., Carobbio S., Masson J., Gaisler-Salomon I., Maechler P., Rayport S., Sluimer J.C., Biessen E.A.L., Guinamard R.R., Gautier E.L., Thorp E.B., Artyomov M.N., Yvan-Charvet L.
פורסם ב: Nature Metabolism
תיאור: 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 glutamate dehydrogenase to fuel ɑ-ketoglutarate-dependent immunometabolism. This pathway is necessary to meet the unique requirements of efferocytosis for cellular detoxification and high-energy cytoskeletal rearrangements. Thus, we uncover a role for non-canonical glutamine metabolism for efficient clearance of dying cells and maintenance of tissue homeostasis during health and disease in mouse and humans. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
SDGs : SDG 03  |  יחידות: מדעי החברה  | מועד: 2021 |  קישור