PXD043071

PXD043071 is an original dataset announced via ProteomeXchange.

Title	ROS-induced ribosome stalling and collision underlies ZAKalpha-mediated metabolic decline in obesity and aging
Description	The ribotoxic stress response (RSR) denotes a signaling pathway in which the p38 and JNK-activating MAP3 kinase ZAKalpha senses stalling and/or collision of ribosomes with unknown physiological implications. Here, we show that reactive oxygen species (ROS)-generating agents robustly trigger translational impairment and ZAKalpha activation. Underscoring the physiological importance of this signaling pathway, zebrafish larvae deficient for the ZAKalpha kinase are protected from ROS-induced pathology and death. Furthermore, livers of mice fed a ROS-generating and obesogenic diet exhibit ZAKalpha-activating changes in ribosomal elongation dynamics. Highlighting a role for the RSR in metabolic regulation, ZAK knockout (KO) mice are protected from developing high-fat diet-induced blood glucose intolerance and liver steatosis under these conditions. Finally, ZAK ablation slows animals from developing hallmarks of metabolic aging. In sum, our work highlights ROS-induced translational impairment as a physiological activation signal for ZAKalpha that underlies metabolic adaptation in obesity and aging.
HostingRepository	PRIDE
AnnounceDate	2024-02-01
AnnouncementXML	Submission_2024-02-01_03:16:36.693.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ana Martinez-Val
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-17 09:53:15	ID requested
⏵ 1	2024-02-01 03:16:37	announced

10.1126/SCIENCE.ADF3208;

submitter keyword: Mouse, obesity, ZAKalpha, Liver

Jesper V. Olsen
contact affiliation	Vice Director, Professor Novo Nordisk Foundation Center for Protein Research Proteomics Program University of Copenhagen Faculty of Health and Medical Sciences Blegdamsvej 3b DK-2200 Copenhagen Denmark
contact email	jesper.olsen@cpr.ku.dk
lab head
Ana Martinez-Val
contact affiliation	Novo Nordisk Foundation Center for Protein Research
contact email	ana.mdval@cpr.ku.dk
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/2024/02/PXD043071

PRIDE project URI

• PRIDE
  1. PXD043071
     1. Label: PRIDE project
     2. Name: ROS-induced ribosome stalling and collision underlies ZAKalpha-mediated metabolic decline in obesity and aging