Peroxisomes are critical for a unique metabolic demand and survival of alveolar macrophages
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Date
2025-05-27
Publication Type
Journal Article
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Abstract
Tissue-resident macrophages (TRMs) populate throughout various tissues, and their homeostatic metabolism is heavily influenced by these microenvironments. Peroxisomes are organelles that contribute to lipid metabolism. However, the involvement of these organelles in the bioenergetics of TRMs remains undetermined. We conducted a developmental screen of TRMs using a conditional peroxisomal biogenesis factor 5 (Pex5) knockout mouse model that lacks functional peroxisomes in all immune cell subsets. Pulmonary alveolar macrophages (AMs) appeared as the only subset of TRMs that required functional peroxisomes for their development. Pex5 deficiency resulted in reduced AM survival due to increased sensitivity to lipotoxicity, in line with an excess accumulation of ceramides. The absence of peroxisomes had a significant effect on overall mitochondrial fitness and altered their metabolic program, allowing them to engage in glycolysis in addition to oxidative phosphorylation. Our results revealed that AMs have a unique metabolic regulation, where peroxisomes play a central role in their homeostatic development and maintenance.
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published
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Volume
44 (5)
Pages / Article No.
115623
Publisher
Cell Press
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Organisational unit
08839 - Zamboni, Nicola (Tit.-Prof.)
02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
Notes
Funding
182829 - Identification of PPARg target genes in macrophages and characterization of their functional roles (SNF)