PXD015644

PXD015644 is an original dataset announced via ProteomeXchange.

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

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.

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;

submitter keyword: mitophagy,WRN, NAD+, NMNAT1, aging

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

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/2020/01/PXD015644

PRIDE project URI

• PRIDE
  1. PXD015644
     1. Label: PRIDE project
     2. Name: NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome