Merlin 2021 Nat Metab

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 JC, Carobbio S, Masson J, Gaisler-Salomon I, Maechler P, Rayport S, Sluimer JC, Biessen EAL, Guinamard RR, Gautier EL, Thorp EB, Artyomov MN, Yvan-Charvet L (2021) Non-canonical glutamine transamination sustains efferocytosis by coupling redox buffering to oxidative phosphorylation. Nat Metab 3:1313-26. https://doi.org/10.1038/s42255-021-00471-y

» PMID: 34650273 Open Access

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 JC, Carobbio S, Masson J, Gaisler-Salomon I, Maechler P, Rayport S, Sluimer JC, Biessen EAL, Guinamard RR, Gautier EL, Thorp EB, Artyomov MN, Yvan-Charvet L (2021) Nat Metab

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 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.

• Bioblast editor: Gnaiger E

Correction: FADH₂ and Complex II

FADH₂ is shown as the substrate feeding electrons into Complex II (CII). This is wrong and requires correction - for details see Gnaiger (2024).

Gnaiger E (2024) Complex II ambiguities ― FADH₂ in the electron transfer system. J Biol Chem 300:105470. https://doi.org/10.1016/j.jbc.2023.105470 - »Bioblast link«

Labels:

Enzyme: Complex II;succinate dehydrogenase