Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation. / Irazoki, Andrea; Gordaliza-Alaguero, Isabel; Frank, Emma; Giakoumakis, Nikolaos Nikiforos; Seco, Jordi; Palacín, Manuel; Gumà, Anna; Sylow, Lykke; Sebastián, David; Zorzano, Antonio.

In: Nature Communications, Vol. 14, No. 1, 108, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Irazoki, A, Gordaliza-Alaguero, I, Frank, E, Giakoumakis, NN, Seco, J, Palacín, M, Gumà, A, Sylow, L, Sebastián, D & Zorzano, A 2023, 'Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation', Nature Communications, vol. 14, no. 1, 108. https://doi.org/10.1038/s41467-022-35732-1

APA

Irazoki, A., Gordaliza-Alaguero, I., Frank, E., Giakoumakis, N. N., Seco, J., Palacín, M., Gumà, A., Sylow, L., Sebastián, D., & Zorzano, A. (2023). Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation. Nature Communications, 14(1), [108]. https://doi.org/10.1038/s41467-022-35732-1

Vancouver

Irazoki A, Gordaliza-Alaguero I, Frank E, Giakoumakis NN, Seco J, Palacín M et al. Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation. Nature Communications. 2023;14(1). 108. https://doi.org/10.1038/s41467-022-35732-1

Author

Irazoki, Andrea ; Gordaliza-Alaguero, Isabel ; Frank, Emma ; Giakoumakis, Nikolaos Nikiforos ; Seco, Jordi ; Palacín, Manuel ; Gumà, Anna ; Sylow, Lykke ; Sebastián, David ; Zorzano, Antonio. / Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation. In: Nature Communications. 2023 ; Vol. 14, No. 1.

Bibtex

@article{22f69b581a7349dba1320d56653074bb,

title = "Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation",

abstract = "Some forms of mitochondrial dysfunction induce sterile inflammation through mitochondrial DNA recognition by intracellular DNA sensors. However, the involvement of mitochondrial dynamics in 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.",

author = "Andrea Irazoki and Isabel Gordaliza-Alaguero and Emma Frank and Giakoumakis, {Nikolaos Nikiforos} and Jordi Seco and Manuel Palac{\'i}n and Anna Gum{\`a} and Lykke Sylow and David Sebasti{\'a}n and Antonio Zorzano",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

doi = "10.1038/s41467-022-35732-1",

language = "English",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

number = "1",

}

RIS

TY - JOUR

T1 - Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation

AU - Irazoki, Andrea

AU - Gordaliza-Alaguero, Isabel

AU - Frank, Emma

AU - Giakoumakis, Nikolaos Nikiforos

AU - Seco, Jordi

AU - Palacín, Manuel

AU - Gumà, Anna

AU - Sylow, Lykke

AU - Sebastián, David

AU - Zorzano, Antonio

PY - 2023

Y1 - 2023

N2 - Some forms of mitochondrial dysfunction induce sterile inflammation through mitochondrial DNA recognition by intracellular DNA sensors. However, the involvement of mitochondrial dynamics in 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.

AB - Some forms of mitochondrial dysfunction induce sterile inflammation through mitochondrial DNA recognition by intracellular DNA sensors. However, the involvement of mitochondrial dynamics in 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.

UR - http://www.scopus.com/inward/record.url?scp=85145718299&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-35732-1

DO - 10.1038/s41467-022-35732-1

M3 - Journal article

C2 - 36609505

AN - SCOPUS:85145718299

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 108

ER -

ID: 332191456

Department of Biomedical Sciences