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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/186126
Mitochondrial dynamics as a hub in the control of muscle inflammation
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[eng] Some forms of mitochondrial dysfunction induce sterile inflammation through mitochondrial DNA (mtDNA) recognition by intracellular DNA sensors. However, our understanding of the processes operating this activation is partial. Here we have analyzed the participation of mitochondrial dynamics in the control of inflammatory responses. We document that mitochondrial fragmentation causes NFκB-dependent inflammation, whereas mitochondrial elongation activates both NFκB and type I interferon (IFN) inflammatory responses in muscle cells. This differential response is a consequence of activation of the DNA sensors TLR9 or cGAS. Surprisingly, we also document that Mfn1 deficiency-induced inflammation is associated with an enhanced encounter of mitochondria with early endosomes, which requires the participation of the early endosomal protein Rab5C. Mfn1 ablation in mouse skeletal muscles promoted NFκB activation, muscle atrophy, reduced physical performance and enhanced IL6 response to exercise, which were improved or rescued upon chronic anti- inflammatory treatment.
Taken together, our data demonstrate that mitochondrial dynamics is key in mitigating different inflammatory responses through mtDNA mislocation. We also demonstrate that muscle inflammation caused by mitochondrial fragmentation precedes the development of muscle atrophy and impaired physical performance. Therefore, we propose that inflammatory muscle disorders characterized by triggering of DNA sensors can be underpinned by therapeutic strategies promoting balanced mitochondrial dynamics.
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IRAZOQUI GUIMON, Andrea. Mitochondrial dynamics as a hub in the control of muscle inflammation. [consulta: 9 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/186126]