Clayton, S. A. et al. (2021) Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48. Science Advances, 7(50), eabl5182. (doi: 10.1126/sciadv.abl5182) (PMID:34878835)
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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.
Item Type: | Articles |
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Additional Information: | This work was supported by Programme Grant 21802 and Research into Inflammatory Arthritis Centre Versus Arthritis (22072), both from Versus Arthritis, UK |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Kurowska-Stolarska, Professor Mariola and Elmesmari, Dr Aziza and Woolcock, Mr Kieran and Fernandez-Vizarra, Dr Erika and Buckley, Professor Christopher and Filer, Dr Andrew and MacDonald, Miss Lucy and Alivernini, Mr Stefano and Goodyear, Professor Carl |
Authors: | Clayton, S. A., Daley, K. K., MacDonald, L., Fernandez-Vizarra, E., Bottegoni, G., O’Neil, J. D., Major, T., Griffin, D., Zhuang, Q., Adewoye, A. B., Woolcock, K., Jones, S. W., Goodyear, C., Elmesmari, A., Filer, A., Tennant, D. A., Alivernini, S., Buckley, C. D., Pitceathly, R. D. S., Kurowska-Stolarska, M., and Clark, A. R. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
Journal Name: | Science Advances |
Publisher: | American Association for the Advancement of Science |
ISSN: | 2375-2548 |
ISSN (Online): | 2375-2548 |
Published Online: | 08 December 2021 |
Copyright Holders: | Copyright © 2021 The Authors |
First Published: | First published in Science Advances 7(50): eabl5182 |
Publisher Policy: | Reproduced under a Creative Commons License |
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