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PXD041993

PXD041993 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePhospholipids with two polyunsaturated fatty acyl tails drive ferroptosi.
DescriptionPhospholipids 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.
HostingRepositoryPRIDE
AnnounceDate2025-05-06
AnnouncementXMLSubmission_2025-05-06_09:27:01.666.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRajesh Soni
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro 2
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-04 16:28:41ID requested
12025-05-06 09:27:02announced
Publication List
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;
Keyword List
submitter keyword: Polyunsaturated fatty acid
PUFA
phospholipid
mitochondria
complex I
ROS
ferroptosis
lipids
Contact List
Brent R. Stockwell
contact affiliationDepartment of Chemistry, Columbia University, New York, NY 10027
contact emailbstockwell@columbia.edu
lab head
Rajesh Soni
contact affiliationColumbia University Medical center
contact emailrs3869@cumc.columbia.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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