PXD069869

PXD069869 is an original dataset announced via ProteomeXchange.

Title	Polyunsaturated fatty acid sequestration protects against ferroptosis in mitochondrial dysfunction
Description	While impaired energy production is a hallmark of mitochondrial oxidative phosphorylation (OXPHOS) defects, many OXPHOS aberrations permit residual energy output, leading to pathologies driven by secondary metabolic disturbances, such as redox stress. We have discovered that cells with OXPHOS deficiencies accumulate triacylglycerols enriched in polyunsaturated fatty acids (PUFAs), which are stored in lipid droplets. Sequestration of PUFAs is a critical component of a broader stress response, which also includes downregulation of cellular desaturases and upregulation of glutathione peroxidase 4 (GPX4). Here, we demonstrate that this mechanism represents a physiologically relevant protective strategy, manifesting in the cells under hypoxia and fibroblasts derived from patients with primary mitochondrial complex IV deficiency. As proof of principle, we observed elevated PUFA-enriched triacylglycerols in the plasma of patients with Myoclonic Epilepsy with Ragged Red Fibres (MERRF). Our findings reveal a novel protective mechanism against ferroptosis, which preserves membrane integrity when mitochondrial respiration is compromised.
HostingRepository	PRIDE
AnnounceDate	2026-07-12
AnnouncementXML	Submission_2026-07-12_15:41:02.457.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marek Vrbacky
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	methylthiolated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-24 00:13:40	ID requested
⏵ 1	2026-07-12 15:41:02	announced

Dataset with its publication pending

submitter keyword: None

Alena Pecinova
contact affiliation	Laboratory of Bioenergetics, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
contact email	alena.pecinova@fgu.cas.cz
lab head
Marek Vrbacky
contact affiliation	Czech Academy of Sciences
contact email	proteom.krc@gmail.com
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/2026/07/PXD069869

PRIDE project URI

• PRIDE
  1. PXD069869
     1. Label: PRIDE project
     2. Name: Polyunsaturated fatty acid sequestration protects against ferroptosis in mitochondrial dysfunction