PXD041993 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-05-04 16:28:41 | ID requested | |
⏵ 1 | 2025-05-06 09:27:02 | announced | |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD041993
- Label: PRIDE project
- Name: Phospholipids with two polyunsaturated fatty acyl tails drive ferroptosi.