Selenoprotein o as a regulator of macrophage metabolism in selenium deficiency-induced lung inflammation

• Published in: International journal of biological macromolecules 2024-11, Vol.281 (Pt 1), p.136232, Article 136232
• Main Authors: Du, Yongzhen, Xia, Yu, Xu, Tong, Hu, Haojie, He, Yujiao, Zhang, Muyue, Li, Shu
• Format: Article
• Language: English
• Subjects: Animals; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Energy Metabolism; Gene Knockdown Techniques; High Mobility Group Proteins; Macrophage polarization; Macrophages - metabolism; Macrophages, Alveolar - metabolism; Male; Metabolic reprogramming; Mice; Mice, Inbred C57BL; Mitochondria - metabolism; Oxidative Phosphorylation; Pneumonia - genetics; Pneumonia - metabolism; Pneumonia - pathology; Pulmonary inflammation; Se deficiency; Selenium - deficiency; Selenium - metabolism; Selenoprotein O; Selenoproteins - genetics; Selenoproteins - metabolism; TFAM; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.136232

Selenium (Se) deficiency induces an inflammatory response in the lungs, but the underlying mechanisms are unknown. Selenoprotein O (SelO) is the largest selenoprotein in terms of molecular weight, yet its potential biological functions have yet to be characterized. Our study revealed that Se deficiency leads to an imbalance in the expression of pro-inflammatory “M1” macrophages and anti-inflammatory “M2” macrophages in alveolar macrophages (AMs) and interstitial macrophages (IMs) and contributed to the development of lung inflammation. Through the analysis of differentially expressed selenoproteins, we identified SelO as a potential regulator of the imbalance in pulmonary macrophage polarization caused by Se deficiency. In vitro experiments showed that SelO knockdown enhanced the polarization of M1 macrophages while suppressing that of M2 macrophages. In addition, SelO knockdown reprogrammed macrophage metabolism to glycolysis, disrupting oxidative phosphorylation (OXPHOS). Mechanistically, SelO primarily targets mitochondrial transcription factor A (TFAM), which plays a crucial role in the transcription and replication of mitochondrial DNA (mtDNA) and is essential for mitochondrial biogenesis and energy metabolism. The deficiency of SelO affects TFAM, resulting in its uncontrolled degradation, which compromises mitochondrial function and energy metabolism. In summary, the findings presented here offer significant theoretical insights into the physiological functions of SelO. [Display omitted] •Se deficiency induces macrophage M1/M2 polarization imbalance in broiler lungs.•SelO is the main mediator of Se deficiency-induced macrophage polarization imbalance.•SelO knockdown promotes M1 polarization and inhibits M2 polarization in macrophages.•SelO deficiency leads to uncontrolled degradation of TFAM in macrophages.•SelO regulates macrophage metabolic reprogramming mitochondrial function via TFAM.