PXD044595

PXD044595 is an original dataset announced via ProteomeXchange.

Title	HSF-1 promotes longevity through ubiquilin-1 dependent mitochondrial remodelling
Description	Impaired protein homeostasis promotes age-associated tissue dysregulation, presenting a need for therapeutic approaches that can restore proteome integrity. The heat shock factor HSF-1 is the master transcriptional regulator of proteostasis and regulates the expression of heat shock proteins (HSPs), which facilitate proper protein folding, localisation, and degradation. Increased HSF-1 activity can suppress proteotoxicity and enhance longevity across species. Studies into the mechanisms behind these beneficial effects have mostly focused on HSPs; however, the precise mechanisms by which increased HSF-1 activity extends lifespan are not known. To address this, we conducted an RNAi screen for genes that promote longevity, in C. elegans over expressing HSF-1 (hsf-1 OE). We found that ubiquilin-1 (ubql-1), a multifaceted shuttle protein that functions in protein degradation pathways is necessary for full lifespan extension in hsf-1OE worms. Surprisingly, we find that lack of ubql-1 does not impact proteostasis capacity, but does alter mitochondrial dynamics, in hsf-1 OE worms. These effects are independent of mitophagy or the mitochondrial unfolded protein response (mitoUPR) suggesting enhanced turnover of mitochondrial outer membrane proteins may be important for increased longevity via the HSF-1-ubiquilin-1 axis. Additionally, we reveal a role for ubql-1, a protein quality control regulator in regulating lipid homeostasis in hsf-1 OE animals. Lack of ubql-1 in hsf-1 OE animals supresses the expression of a key mitochondrial β-oxidation and lipid mobilization gene regulated by NHR-49 - acyl-CoA synthetase-2, ACS-2 amongst other genes. We propose that ubql-1 is required for mito-fusion and metabolic modulations that promote longevity in hsf-1 OE by interacting with NHR-49.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_07:48:27.800.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	riccardo zenezini chiozzi
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-15 09:57:24	ID requested
⏵ 1	2024-10-17 07:48:28	announced

Dataset with its publication pending

submitter keyword: HSF-1

aging

proteomics;

John Labbadia
contact affiliation	Institute of Healthy Ageing, UCL Department of Genetics, Evolution and Environment, London, WC1E 6BT
contact email	j.labbadia@ucl.ac.uk
lab head
riccardo zenezini chiozzi
contact affiliation	UCL
contact email	r.chiozzi@ucl.ac.uk
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/2024/10/PXD044595

PRIDE project URI

• PRIDE
  1. PXD044595
     1. Label: PRIDE project
     2. Name: HSF-1 promotes longevity through ubiquilin-1 dependent mitochondrial remodelling