In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 7, No. 50 ( 2021-12-10)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2375-2548
DOI:
10.1126/sciadv.abl5182
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2021
detail.hit.zdb_id:
2810933-8
Bookmarklink