Non-canonical glutamine transamination sustains efferocytosis by coupling redox buffering to oxidative phosphorylation.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
28
09
2020
accepted:
06
09
2021
pubmed:
16
10
2021
medline:
15
12
2021
entrez:
15
10
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34650273
doi: 10.1038/s42255-021-00471-y
pii: 10.1038/s42255-021-00471-y
pmc: PMC7611882
mid: EMS134114
doi:
Substances chimiques
Glutamine
0RH81L854J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1313-1326Subventions
Organisme : European Research Council
ID : 724838
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL122309
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL159964
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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