Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/192160
Title: | Dysruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation |
Author: | Irazoki, A. Gordaliza-Alaguero, Isabel Frank, Emma Giakoumakis, Nikolaos Nikiforos Seco, Jordi Palacín Prieto, Manuel Gumà i Garcia, Anna Maria Sylow, Lykke Sebastián Muñoz, David Zorzano Olarte, Antonio |
Keywords: | ADN mitocondrial Mitocondris Malalties musculars ADN Envelliment Inflamació Mitochondrial DNA Mitochondria Muscular Diseases DNA Aging Inflammation |
Issue Date: | 6-Jan-2023 |
Publisher: | Nature Publishing Group |
Abstract: | Some forms of mitochondrial dysfunction induce sterile inflammation through mitochondrial DNA (mtDNA) recognition by intracellular DNA sensors. However, the involvement of mitochondrial dynamics mitigating such processes and their impact on muscle fitness remain unaddressed. Here we report that opposite mitochondrial morphologies induce distinct inflammatory signatures, caused by differential activation of DNA sensors TLR9 or cGAS. In the context of mitochondrial fragmentation, we demonstrate that mitochondria-endosome contacts mediated by the endosomal protein Rab5C are required in TLR9 activation in cells. Skeletal muscle mitochondrial fragmentation promotes TLR9-dependent inflammation, muscle atrophy, reduced physical performance and enhanced IL6 response to exercise, which improved upon chronic anti-inflammatory treatment. Taken together, our data demonstrate that mitochondrial dynamics is key in preventing sterile inflammatory responses, which precede the development of muscle atrophy and impaired physical performance. Thus, we propose the targeting of mitochondrial dynamics as an approach to treating disorders characterized by chronic inflammation and mitochondrial dysfunction. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-022-35732-1 |
It is part of: | Nature Communications, 2023, vol. 14 (1), num. 108, p. 1-19 |
URI: | http://hdl.handle.net/2445/192160 |
Related resource: | https://doi.org/10.1038/s41467-022-35732-1 |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Bioquímica i Fisiologia) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
727427.pdf | 5.57 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License