The epithelial C15ORF48/miR-147-NDUFA4 axis is an essential regulator of gut inflammation, energy metabolism, and the microbiome
Abstract
Significance Emerging evidence emphasizes the significance of mitochondrial metabolism reprograming in the gut epithelium for regulating intestinal inflammation. Nevertheless, the intricate mechanisms underpinning this connection remain elusive. We have uncovered the predominant expression of C15ORF48/miR-147 in the gut epithelium and conducted an in vivo investigation of its functions. Our findings suggest that epithelial C15ORF48/miR-147 safeguards against aberrant gut inflammation and dysbiosis. Mechanistically, through its two molecular products—C15ORF48 protein and miR-147-3p miRNA—C15ORF48/miR-147 silences NDUFA4, a mitochondrial complex IV subunit. Notably, NDUFA4 not only impacts mitochondrial respiration but also controls inflammation signaling. This establishes the C15ORF48/miR-147-NDUFA4 molecular axis as an essential controller of gut homeostasis, linking energy metabolism and inflammation. These insights hold promise for innovative therapies against gastrointestinal diseases.
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