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PXD015644

PXD015644 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome
DescriptionMetabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD+, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models. WRN regulates transcription of a key NAD+ biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1). NAD+ repletion restores NAD+ metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD+ repletion remarkably extends lifespan and delays accelerated aging, including stem cell dysfunction, in C. elegans and Drosophila melanogaster models of WS. Our findings suggest that accelerated aging in WRN syndrome is mediated by impaired mitochondrial function and mitophagy, and that bolstering cellular NAD+ levels counteracts WS phenotypes.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:09:28.979.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristian Koehler
SpeciesList scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-09-30 06:29:45ID requested
12020-01-13 05:49:49announced
22024-10-22 04:09:29announced2024-10-22: Updated project metadata.
Publication List
Fang EF, Hou Y, Lautrup S, Jensen MB, Yang B, SenGupta T, Caponio D, Khezri R, Demarest TG, Aman Y, Figueroa D, Morevati M, Lee HJ, Kato H, Kassahun H, Lee JH, Filippelli D, Okur MN, Mangerich A, Croteau DL, Maezawa Y, Lyssiotis CA, Tao J, Yokote K, Rusten TE, Mattson MP, Jasper H, Nilsen H, Bohr VA, augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun, 10(1):5284(2019) [pubmed]
10.1038/s41467-019-13172-8;
Keyword List
submitter keyword: mitophagy,WRN, NAD+, NMNAT1, aging
Contact List
Bernd Thiede
contact affiliationDepartment of Biosciences, Univesity of Oslo
contact emailbernd.thiede@ibv.uio.no
lab head
Christian Koehler
contact affiliationUniversity of Oslo
contact emailchristian.koehler@ibv.uio.no
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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