PXD037935

PXD037935 is an original dataset announced via ProteomeXchange.

Title	Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mtDNA mislocation
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:24:25.685.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marta Vilaseca
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-03 05:03:14	ID requested
1	2023-01-20 05:41:24	announced
⏵ 2	2023-11-14 08:24:26	announced	2023-11-14: Updated project metadata.

Irazoki A, Gordaliza-Alaguero I, Frank E, Giakoumakis NN, Seco J, Palac, í, n M, Gum, à A, Sylow L, Sebasti, á, n D, Zorzano A, Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation. Nat Commun, 14(1):108(2023) [pubmed]

submitter keyword: mtDNA, inflammation, DNA sensors, endosomes,mitochondrial dynamics, muscle, atrophy

Antonio Zorzano
contact affiliation	Institute for Research in Biomedicine, Baldiri i Reixac 10, Barcelona 08028, Spain. Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) Instituto de Salud Carlos III, Spain.
contact email	antonio.zorzano@irbbarcelona.org
lab head
Marta Vilaseca
contact affiliation	Mass Spectrometry & Proteomics Core Facility (MSPCF) Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology (BIST) C/ Baldiri Reixac, 10-12 08028 Barcelona - Spain
contact email	masspe@irbbarcelona.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/01/PXD037935

PRIDE project URI

• PRIDE
  1. PXD037935
     1. Label: PRIDE project
     2. Name: Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mtDNA mislocation