Peroxisomes are critical for a unique metabolic demand and survival of alveolar macrophages.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-05-27 Epub Date: 2025-04-25 DOI:10.1016/j.celrep.2025.115623

Mai Matsushita, Jonathan Muri, Ivan Berest, Fengqi Li, Huan Liu, Basak Corak, Nicola Zamboni, Joerg Buescher, Alaa Othman, Mauro Corrado, Jovana Cupovic, Sabine Werner, Werner Kovacs, Manfred Kopf

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引用次数: 0

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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过氧化物酶体是肺泡巨噬细胞独特的代谢需求和生存的关键。

组织常驻巨噬细胞（TRMs）遍布各种组织，它们的稳态代谢受到这些微环境的严重影响。过氧化物酶体是参与脂质代谢的细胞器。然而，这些细胞器在trm生物能量学中的作用仍未确定。我们使用在所有免疫细胞亚群中缺乏功能性过氧化物酶体的条件过氧化物酶体生物发生因子5 （Pex5）敲除小鼠模型对trm进行了发育筛选。肺泡巨噬细胞（AMs）似乎是trm中唯一需要功能性过氧化物酶体来发育的子集。由于对脂肪毒性的敏感性增加，Pex5缺乏导致AM存活率降低，这与神经酰胺的过度积累一致。过氧化物酶体的缺失对线粒体的整体适应性产生了重大影响，并改变了它们的代谢程序，使它们能够参与糖酵解和氧化磷酸化。我们的研究结果表明，am具有独特的代谢调节，其中过氧化物酶体在其稳态发育和维持中发挥核心作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.