{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang YT"],"funding":["NIAID NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["316-331.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9908853"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["35(2)"],"pubmed_abstract":["Apoptotic cell (AC) clearance (efferocytosis) is performed by phagocytes, such as macrophages, that inhabit harsh physiological environments. Here, we find that macrophages display enhanced efferocytosis under prolonged (chronic) physiological hypoxia, characterized by increased internalization and accelerated degradation of ACs. Transcriptional and translational analyses revealed that chronic physiological hypoxia induces two distinct but complimentary states. The first, \"primed\" state, consists of concomitant transcription and translation of metabolic programs in AC-naive macrophages that persist during efferocytosis. The second, \"poised\" state, consists of transcription, but not translation, of phagocyte function programs in AC-naive macrophages that are translated during efferocytosis. Mechanistically, macrophages efficiently flux glucose into a noncanonical pentose phosphate pathway (PPP) loop to enhance NADPH production. PPP-derived NADPH directly supports enhanced efferocytosis under physiological hypoxia by ensuring phagolysosomal maturation and redox homeostasis. Thus, macrophages residing under physiological hypoxia adopt states that support cell fitness and ensure performance of essential homeostatic functions rapidly and safely."],"journal":["Cell metabolism"],"pubmed_title":["Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments."],"pmcid":["PMC9908853"],"funding_grant_id":["DP2 GM146337","T32 CA009149","R01 CA248364","P30 CA008748","T32 AI007496","R00 CA237728","L30 CA274750"],"pubmed_authors":["Trzeciak AJ","Keshari KR","Etchegaray JI","Chirayil R","Puleston DJ","Chen YT","Lucas CD","Wang YT","Rojas WS","Perry JSA","Saavedra P"],"additional_accession":[]},"is_claimable":false,"name":"Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments.","description":"Apoptotic cell (AC) clearance (efferocytosis) is performed by phagocytes, such as macrophages, that inhabit harsh physiological environments. Here, we find that macrophages display enhanced efferocytosis under prolonged (chronic) physiological hypoxia, characterized by increased internalization and accelerated degradation of ACs. Transcriptional and translational analyses revealed that chronic physiological hypoxia induces two distinct but complimentary states. The first, \"primed\" state, consists of concomitant transcription and translation of metabolic programs in AC-naive macrophages that persist during efferocytosis. The second, \"poised\" state, consists of transcription, but not translation, of phagocyte function programs in AC-naive macrophages that are translated during efferocytosis. Mechanistically, macrophages efficiently flux glucose into a noncanonical pentose phosphate pathway (PPP) loop to enhance NADPH production. PPP-derived NADPH directly supports enhanced efferocytosis under physiological hypoxia by ensuring phagolysosomal maturation and redox homeostasis. Thus, macrophages residing under physiological hypoxia adopt states that support cell fitness and ensure performance of essential homeostatic functions rapidly and safely.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2025-04-03T23:50:23.315Z","creation":"2025-02-18T23:15:32.475Z"},"accession":"S-EPMC9908853","cross_references":{"pubmed":["36584675"],"doi":["10.1016/j.cmet.2022.12.005"]}}