PXD015644
PXD015644 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome |
Description | Metabolic 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:09:28.979.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Christian Koehler |
SpeciesList | scientific name: Caenorhabditis elegans; NCBI TaxID: 6239; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2019-09-30 06:29:45 | ID requested | |
1 | 2020-01-13 05:49:49 | announced | |
⏵ 2 | 2024-10-22 04:09:29 | announced | 2024-10-22: 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 affiliation | Department of Biosciences, Univesity of Oslo |
contact email | bernd.thiede@ibv.uio.no |
lab head | |
Christian Koehler | |
contact affiliation | University of Oslo |
contact email | christian.koehler@ibv.uio.no |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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