PXD041993

PXD041993 is an original dataset announced via ProteomeXchange.

Title	Phospholipids with two polyunsaturated fatty acyl tails drive ferroptosi.
Description	Phospholipids containing polyunsaturated fatty acyl tails (PL-PUFAs) are susceptible to lipid peroxidation by reactive oxygen species, lipoxygenases, and radical species. The accumulation of peroxidized lipids in cell membranes overwhelms endogenous lipid repair processes and triggers ferroptosis. We discovered that phospholipids with both PUFA tails (PL-PUFA2s) acted as key drivers of ferroptosis in numerous cancer cell lines, compared with phospholipids with a single PUFA tail (PL-PUFA1s), which were substantially less capable of inducing ferroptosis. We found that exogenously supplied phosphatidylcholine with two PUFA tails (PC-PUFA2) was rapidly incorporated into and remodeled membranes in cell lipids. Moreover, PC-PUFA2s were enriched upon free PUFA treatment, suggesting a key role in driving free-PUFA-initiated ferroptosis. We examined the protein-binding profile of PC-PUFA2 and found a specific interaction with the mitochondrial electron transport chain complex I. We confirmed that PC-PUFA2s accumulate in mitochondria and induce production of mitochondrial ROS, which then spread to the endoplasmic reticulum. Depletion of mitochondria through mitophagy eliminated the enhanced potency of PC-PUFA2s over PC-PUFA1s in driving ferroptosis, consistent with mitochondria being the key target of PC-PUFA2s. PC-PUFA2s are thus important lipid markers and drivers of ferroptosis and may serve as future biomarkers and therapeutic targets for modulating ferroptosis in pathological contexts.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:27:01.666.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rajesh Soni
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-04 16:28:41	ID requested
⏵ 1	2025-05-06 09:27:02	announced

Qiu B, Zandkarimi F, Bezjian CT, Reznik E, Soni RK, Gu W, Jiang X, Stockwell BR, Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis. Cell, 187(5):1177-1190.e18(2024) [pubmed]

10.1016/j.cell.2024.01.030;

submitter keyword: Polyunsaturated fatty acid

PUFA

phospholipid

mitochondria

complex I

ROS

ferroptosis

lipids

Brent R. Stockwell
contact affiliation	Department of Chemistry, Columbia University, New York, NY 10027
contact email	bstockwell@columbia.edu
lab head
Rajesh Soni
contact affiliation	Columbia University Medical center
contact email	rs3869@cumc.columbia.edu
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/2025/05/PXD041993

PRIDE project URI

• PRIDE
  1. PXD041993
     1. Label: PRIDE project
     2. Name: Phospholipids with two polyunsaturated fatty acyl tails drive ferroptosi.