PXD018399

PXD018399 is an original dataset announced via ProteomeXchange.

Title	Reduced proteasome activity in the aging brainresults 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 / dis-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 a 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	2020-08-17
AnnouncementXML	Submission_2020-08-16_22:16:50.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joanna Kirkpatrick
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Nothobranchius furzeri; NCBI TaxID: 105023;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-06 02:21:01	ID requested
⏵ 1	2020-08-16 22:16:51	announced

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]

submitter keyword: Aging brain, proteasome activity, aggregation, ribosome stoichiometry

Alessandro Ori
contact affiliation	FLI Leibniz Institute on Aging, Beutenbergstr 11, 07745, Jena, Germany
contact email	alessandro.ori@leibniz-fli.de
lab head
Joanna Kirkpatrick
contact affiliation	The Francis Crick Institute
contact email	joanna.kirkpatrick@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/2020/08/PXD018399

PRIDE project URI

• PRIDE
  1. PXD018399
     1. Label: PRIDE project
     2. Name: Reduced proteasome activity in the aging brainresults in ribosome stoichiometry loss and aggregation