PXD016587

PXD016587 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	2020-06-22
AnnouncementXML	Submission_2020-06-21_23:15:45.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Erika Kelmer Sacramento
SpeciesList	scientific name: Olea europaea (Common olive); NCBI TaxID: 4146; scientific name: Pan troglodytes (Chimpanzee); NCBI TaxID: 9598; scientific name: Vitis vinifera (Grape); NCBI TaxID: 29760; scientific name: Ricinus communis (Castor bean); NCBI TaxID: 3988; scientific name: Vigna mungo (Rice bean) (Black gram); NCBI TaxID: 3915; scientific name: Mesocricetus auratus (Golden hamster); NCBI TaxID: 10036; scientific name: Taeniopygia guttata (Zebra finch) (Poephila guttata); NCBI TaxID: 59729; scientific name: Rattus rattus (Black rat); NCBI TaxID: 10117; scientific name: Solanum tuberosum (Potato); NCBI TaxID: 4113; scientific name: Triticum aestivum (Wheat); NCBI TaxID: 4565; scientific name: Trypanosoma brucei; NCBI TaxID: 5691; scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Merluccius bilinearis (Silver hake); NCBI TaxID: 79698; scientific name: Yarrowia lipolytica (Candida lipolytica); NCBI TaxID: 4952; scientific name: Pongo pygmaeus (Bornean orangutan); NCBI TaxID: 9600; scientific name: Rice(O. sativa); NCBI TaxID: 4530; scientific name: Pisum sativum (Garden pea); NCBI TaxID: 3888; scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825; scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; scientific name: Staphylococcus aureus; NCBI TaxID: 1280; scientific name: Nicotiana tabacum (Common tobacco); NCBI TaxID: 4097; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932; scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355; scientific name: Nothobranchius furzeri; NCBI TaxID: 105023; scientific name: Pinus radiata (Monterey pine); NCBI TaxID: 3347; scientific name: Zea mays (Maize); NCBI TaxID: 4577; scientific name: Struthio camelus (Ostrich); NCBI TaxID: 8801;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-04 04:14:02	ID requested
⏵ 1	2020-06-21 23:15:46	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]

curator keyword: Biological

submitter keyword: Aging, brain, protein complex, aggregation, proteome, transcriptome, proteasome, ribosome, 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/PXD016587

PRIDE project URI

• PRIDE
  1. PXD016587
     1. Label: PRIDE project
     2. Name: Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation