PXD039881-1

PXD039881 is an original dataset announced via ProteomeXchange.

Title	Iron limitation restores autophagy and increases lifespan in the yeast model of Niemann-Pick type C1
Description	Niemann Pick Type C1 (NPC1) is an endolysosomal transmembrane protein involved in the export of cholesterol and sphingolipids to other cellular compartments such as the endoplasmic reticulum and plasma membrane. NPC1 loss of function is the major cause of NPC disease, a rare lysosomal storage disorder characterized by an abnormal accumulation of lipids in the late endosomal/lysosomal network, mitochondrial dysfunction, and impaired autophagy. NPC phenotypes are conserved in yeast lacking Ncr1, orthologue of human NPC1, leading to premature ageing. Herein, we performed a phosphoproteomic analysis to investigate the effect of Ncr1 loss on cellular functions mediated by the yeast lysosome-like vacuoles. Our results revealed changes in vacuolar membrane proteins that are associated mostly with vesicle biology (fusion, transport, organization), autophagy and ion homeostasis, including iron, manganese, and calcium. Consistently, the Cytoplasm to vacuole targeting (Cvt) pathway was increased in ncr1∆ cells and autophagy was compromised despite TORC1 inhibition. Moreover, ncr1∆ cells exhibited iron overload mediated by the low‑iron sensing transcription factor Aft1. Iron deprivation restored the autophagic flux of ncr1∆ cells and increased its chronological lifespan and oxidative stress resistance. These results implicate iron overload on autophagy impairment, oxidative stress sensitivity and cell death in the yeast model of NPC1.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:59:21.425.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hugo Osorio
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-06 02:59:35	ID requested
⏵ 1	2023-11-14 08:59:21	announced

Dataset with its publication pending

submitter keyword: Ncr1

TORC1

Aft1

vacuoles

vesicle trafficking

iron

autophagy

oxidative stress

chronological aging

Vítor Costa
contact affiliation	1- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal 2- IBMC - Instituto de Biologia Celular e Molecular, Universidade do Porto, Portugal 3- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal
contact email	vcosta@ibmc.up.pt
lab head
Hugo Osorio
contact affiliation	i3S - Institute for Research and Innovation in Health, University of Porto
contact email	hosorio@i3s.up.pt
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/2023/03/PXD039881

PRIDE project URI

• PRIDE
  1. PXD039881
     1. Label: PRIDE project
     2. Name: Iron limitation restores autophagy and increases lifespan in the yeast model of Niemann-Pick type C1