Description Exchange of mitochondrial subunits C15ORF48 and NDUFA4 occurs during macrophage activation in vitro and in inflammatory disease. Dysregulated mitochondrial function is a hallmark of immune-mediated inflammatory diseases. Cytochrome c oxidase (C c O), which mediates the rate-limiting step in mitochondrial respiration, is remodeled during development and in response to changes of oxygen availability, but there has been little study of C c O remodeling during inflammation. Here, we describe an elegant molecular switch mediated by the bifunctional transcript C15orf48 , which orchestrates the substitution of the C c O subunit NDUFA4 by its paralog C15ORF48 in primary macrophages. Expression of C15orf48 is a conserved response to inflammatory signals and occurs in many immune-related pathologies. In rheumatoid arthritis, C15orf48 mRNA is elevated in peripheral monocytes and proinflammatory synovial tissue macrophages, and its expression positively correlates with disease severity and declines in remission. C15orf48 is also expressed by pathogenic macrophages in severe coronavirus disease 2019 (COVID-19). Study of a rare metabolic disease syndrome provides evidence that loss of the NDUFA4 subunit supports proinflammatory macrophage functions.
【초록키워드】 COVID-19, Inflammation, Macrophage, macrophages, disease severity, oxygen, in vitro, rheumatoid arthritis, monocyte, proinflammatory, mRNA, metabolic disease, molecular, Pathologies, expression, change, macrophage activation, Evidence, Decline, mitochondrial, Support, Immune-mediated inflammatory diseases, subunit, tissue macrophages, severe coronavirus disease, syndrome, exchange, pathogenic, functions, hallmark, description, inflammatory disease, transcript, Mitochondrial function, cytochrome, NDUFA4, conserved, elevated, provide, occur, expressed, C15orf48, inflammatory signal, synovial, 【제목키워드】 mitochondrial, cause, C15orf48,