<<< Full experiment listing

PXD030938

PXD030938 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDesmin knock-out cardiomyopathy: a heart on the verge of metabolic crisis
DescriptionBackground: Mutations of the desmin gene cause familial and sporadic cardiomyopathies and myopathies. Previous studies showed that both the lack of desmin and expression of mutated desmin negatively impact on number, structure and function mitochondria implying a metabolic dysfunction as disease promoting factor. Here, we exploited desmin knock-out mice to analyse the general metabolic performance of cardiac tissue. Methods: We analysed left ventricular cardiac muscle tissue derived from six-month-old homozygous desmin knock-out mice as well as wild-type siblings. Employing a multi-method approach comprising morphological, clinical chemistry, biochemical, genetic, and proteomic techniques, we specifically addressed energy, fatty acid, glucose, and amino acid metabolism. Results: We demonstrated that the lack of desmin in left ventricular cardiac tissue led to a significant decrease in the number of mitochondria in conjunction with ultrastructural defects of mitochondria. Analysis of mitochondria-related metabolic pathways revealed significantly impaired processes of fatty acid transport, activation, and catabolism associated with increased blood levels of short, medium, and long chain acyl-carnitines. In addition to increased amounts of glucose transporter 1 and hexokinase 1, we detected a significantly increased hexokinase enzyme activity. While the amount of mitochondrial creatine kinase was markedly reduced, fetal creatine kinase was increased. The picture of a highly dysbalanced metabolic state was complemented by our quantitative proteomic analysis that revealed significantly reduced levels of multiple proteins centrally involved in electron transport mainly of complexes I and II, oxidative phosphorylation, citrate cycle, beta oxidation including auxiliary pathways, amino acid catabolism, and redox reactions and oxidative stress. Conclusions: Our data denoted a picture of widespread metabolic dysfunction far reaching beyond the level of mitochondria in left ventricular cardiac tissue of desmin knock-out mice. The increase of glucose utilisation along with increased level of fetal creatine kinase likely is a compensatory measure counteracting the severely hampered fatty acid metabolism and oxidative phosphorylation. The degree of metabolic disbalance, already observed in desmin knock-out mice kept under standard ‘sedentary’ housing conditions, renders it likely that acute strenuous physical exercise with its steeply increased energy demand will push the cardiac tissue into severe metabolic crisis.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:33:21.536.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBritta Eggers
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-01-13 06:29:20ID requested
12022-10-21 01:44:45announced
22023-11-14 08:33:23announced2023-11-14: Updated project metadata.
Publication List
Elsnicova B, Hornikova D, Tibenska V, Kolar D, Tlapakova T, Schmid B, Mallek M, Eggers B, Schl, ö, tzer-Schrehardt U, Peeva V, Berwanger C, Eberhard B, Durmu, ş H, Schultheis D, Holtzhausen C, Schork K, Marcus K, Jordan J, L, ü, cke T, van der Ven PFM, Schr, ö, der R, Clemen CS, Zurmanova JM, Desmin Knock-Out Cardiomyopathy: A Heart on the Verge of Metabolic Crisis. Int J Mol Sci, 23(19):(2022) [pubmed]
Keyword List
submitter keyword: metabolism, fatty acid,desmin, mitochondria, glucose, desminopathy, desmin knock-out, creatine kinase, cardiomyopathy, amino acid
Contact List
Prof. Dr. Katrin Marcus
contact affiliationMedizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, Bochum, Germany, Medical Proteome Analysis, Center for Proteindiagnostics (PRODI), Ruhr-University Bochum, Bochum, Germany
contact emailkatrin.marcus@rub.de
lab head
Britta Eggers
contact affiliationRuhr University Bochum
contact emailbritta.eggers@rub.de
dataset submitter
Full Dataset Link List
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/2022/10/PXD030938
PRIDE project URI
Repository Record List
[ + ]