Mitochondrial Regulator CRIF1 Plays a Critical Role in the Development and Homeostasis of Alveolar Macrophages via Maintaining Metabolic Fitness

• DOI: 10.4110/in.2025.25.e9
• Publication Date: 2025-02-28T07:20:13Z
• Authors: Ein Lee; Seung Geun Song; Haaun Moon; Minho Shong; Doo Hyun Chung
• Keywords: Homeostasis

The importance of mitochondrial function in macrophages is well established. Alveolar (AMs), the tissue-resident (TRMs) lung, are particularly dependent on mitochondria-driven oxidative phosphorylation (OXPHOS) to support their functions and maintain homeostasis. However, specific genes pathways that regulate OXPHOS AMs remain unclear. In this study, we investigated role CR6-interacting factor 1 (CRIF1), a regulator, as key specifically modulates metabolic fitness maintenance AMs. Using single-cell RNA sequencing transcriptomic analyses, found CRIF1 be highly expressed compared TRMs from other tissues, correlating with enhanced activity. Genetic ablation Crif1 resulted marked reduction AM populations exclusively while TRM were unaffected. CRIF1-deficient exhibited an altered profile, including impaired function, increased glycolysis, aberrant lipid accumulation. These findings underscore essential regulating AMs, distinguishing it broader regulators like transcription A, which operates across multiple populations. Our study provides critical insights into tissue-specific regulation macrophage metabolism suggests potential therapeutic avenues for lung diseases associated dysfunction.