PXD059629
PXD059629 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Metabolic dysregulation contributes to the development of dysferlinopathy |
| Description | Dysferlin is a transmembrane protein that plays a prominent role in membrane repair of damaged muscle fibers. Accordingly, mutations of the dysferlin gene cause progressive muscular dystrophies, collectively referred to as dysferlinopathies for which no effective treatment exists. Unexpectedly, experimental approaches that successfully restore membrane repair fail to prevent a dystrophic phenotype, suggesting that additional, hitherto unknown dysferlin-dependent functions contribute to the development of the pathology. Our experiments revealed an altered metabolic phenotype in dysferlin-deficient muscles, characterized by 1) mitochondrial abnormalities and elevated death signaling and 2) increased glucose uptake, reduced glycolytic protein levels, and a pronounced glycogen accumulation. Strikingly, elevating mitochondrial volume density and muscle glycogen accelerates disease progression while improvement of mitochondrial function and recruitment of muscle glycogen with exercise ameliorated functional parameters in a mouse model of dysferlinopathy. Collectively, our results not only shed light on a metabolic function of dysferlin, but also imply new therapeutic avenues aimed at promoting mitochondrial function and normalizing muscle glycogen to ameliorate dysferlinopathies, complementing efforts that target membrane repair. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-02-25 |
| AnnouncementXML | Submission_2025-02-25_00:10:02.665.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | danilo ritz |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | Phospho |
| Instrument | Orbitrap Fusion Lumos; timsTOF Ultra |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-01-10 04:30:42 | ID requested | |
| ⏵ 1 | 2025-02-25 00:10:03 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: dysferlinopathy, exercise, glucose metabolism, glycogen, mitochondrial dysfunction muscular dystrophy, PGC-1alpha, DatasetType:Proteomics |
Contact List
| Alexander Schmidt | |
|---|---|
| contact affiliation | Biozentrum, Universtiy of Basel, 4056 Basel, Switzerland |
| contact email | alex.schmidt@unibas.ch |
| lab head | |
| danilo ritz | |
| contact affiliation | University of Basel |
| contact email | danilo.ritz@unibas.ch |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive.ucsd.edu/v06/MSV000096818/ |
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