Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48

Stefano Alivernini, Sally A. Clayton, Kalbinder K. Daley, Lucy Macdonald, Erika Fernandez-Vizarra, Giovanni Bottegoni, John D. O'Neil, Triin Major, Daniel Griffin, Qinqin Zhuang, Adeolu B. Adewoye, Kieran Woolcock, Simon W. Jones, Carl Goodyear, Aziza Elmesmari, Andrew Filer, Daniel A. Tennant, Christopher D. Buckley, Robert D.S. Pitceathly, Mariola Kurowska-StolarskaAndrew R. Clark

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Dysregulated mitochondrial function is a hallmark of immune-mediated inflammatory diseases. Cytochrome c oxidase (CcO), 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 CcO remodeling during inflammation. Here, we describe an elegant molecular switch mediated by the bifunctional transcript C15orf48, which orchestrates the substitution of the CcO 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.
Lingua originaleEnglish
pagine (da-a)eabl5182-N/A
RivistaScience advances
Volume7
DOI
Stato di pubblicazionePubblicato - 2021

Keywords

  • INGLESE

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