PXD016459

PXD016459 is an original dataset announced via ProteomeXchange.

Title	Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation
Description	A progressive loss of protein homeostasis is characteristic of aging and a driver of neurodegeneration. To investigate this process quantitatively, we characterized proteome dynamics during brain aging in the short-lived vertebrate Nothobranchius furzeri combining transcriptomics and proteomics. We detected a progressive reduction in the correlation between protein and mRNA mainly due to post-transcriptional mechanisms that account for over 40% of the age-regulated proteins. These changes cause a progressive loss of stoichiometry in several protein complexes, including ribosomes, which show impaired assembly and are enriched in protein aggregates in old brains. Mechanistically, we show that reduction of proteasome activity is an early event during brain aging and is sufficient to induce proteomic signatures of aging and loss of stoichiometry in vivo. Using longitudinal transcriptomic data, we show that the magnitude of early life decline in proteasome levels is the major risk factor for mortality. Our work defines causative events in the aging process that can be targeted to prevent loss of protein homeostasis and delay the onset of age-related neurodegeneration.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:07:40.705.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Erika Kelmer Sacramento
SpeciesList	scientific name: Nothobranchius furzeri; NCBI TaxID: 105023;
ModificationList	carbamoylated residue; monohydroxylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-27 01:11:27	ID requested
1	2020-06-21 22:30:38	announced
⏵ 2	2024-10-22 05:07:45	announced	2024-10-22: Updated project metadata.

10.15252/msb.20209596;

Kelmer Sacramento E, Kirkpatrick JM, Mazzetto M, Baumgart M, Bartolome A, Di Sanzo S, Caterino C, Sanguanini M, Papaevgeniou N, Lefaki M, Childs D, Bagnoli S, Terzibasi Tozzini E, Di Fraia D, Romanov N, Sudmant PH, Huber W, Chondrogianni N, Vendruscolo M, Cellerino A, Ori A, Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation. Mol Syst Biol, 16(6):e9596(2020) [pubmed]

curator keyword: Biological

submitter keyword: transcriptome, brain, ribosome,Aging, protein complex, proteome, proteasome, aggregation, stoichiometry

Alessandro Ori
contact affiliation	Leibniz Institute on Aging – Fritz Lipmann Institute (FLI), Jena, Germany
contact email	alessandro.ori@leibniz-fli.de
lab head
Erika Kelmer Sacramento
contact affiliation	Leibniz Institute on Aging - Fritz Lipmann Institute
contact email	erika.kelmer@leibniz-fli.de
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/2020/06/PXD016459

PRIDE project URI

• PRIDE
  1. PXD016459
     1. Label: PRIDE project
     2. Name: Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation