Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments Journal Article

   

Authors:	Wang, Y. T.; Trzeciak, A. J.; Rojas, W. S.; Saavedra, P.; Chen, Y. T.; Chirayil, R.; Etchegaray, J. I.; Lucas, C. D.; Puleston, D. J.; Keshari, K. R.; Perry, J. S. A.
Article Title:	Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments
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. © 2022 Elsevier Inc.
Keywords:	metabolism; apoptosis; oxygen; physiology; hypoxia; macrophage; phagocytosis; macrophages; homeostasis; nadp; nicotinamide adenine dinucleotide phosphate; humans; human; cellular adaptation; pentose phosphate pathway; efferocytosis; apoptotic cell clearance; physiological hypoxia
Journal Title:	Cell Metabolism
Volume:	35
Issue:	2
ISSN:	1550-4131
Publisher:	Elsevier Inc.
Date Published:	2023-02-07
Start Page:	316
End Page:	331.e6
Language:	English
DOI:	10.1016/j.cmet.2022.12.005
PUBMED:	36584675
PROVIDER:	scopus
PMCID:	PMC9908853
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85147375146&doi=10.1016%2fj.cmet.2022.12.005&partnerID=40&md5=a5dcadf6bbd6a761b6e119f3d37cf1ae
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Justin S.A. Perry -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/203223