PXD061038-1

PXD061038 is an original dataset announced via ProteomeXchange.

Title	Riboflavin metabolism shapes FSP1-driven ferroptosis resistance
Description	Membrane protection against oxidative damage is tightly buffered by glutathione peroxidase 4 (GPX4), and endogenous radical-trapping antioxidants such as ubiquinone, vitamin E and K. Deficiencies in these protective systems have been linked to the accumulation of phospholipid peroxidation and ferroptosis induction. Recently, ferroptosis suppressor protein 1 (FSP1) was identified as a key player in this process, preventing phospholipid peroxidation and ferroptosis by regenerating radical-trapping antioxidants. Yet, regulators of FSP1 have remained largely unknown, and their identification is critical for understanding the mechanism regulating phospholipid peroxidation and ferroptosis. In this study, we conducted a CRISPR-Cas9 screen to uncover factors influencing FSP1 function, identifying vitamin B2 (riboflavin) as a yet-unaccounted modulator of ferroptosis sensitivity. We demonstrate that vitamin B2, unlike other vitamins that directly act as radical-trapping antioxidants, facilitates the recycling of lipid-soluble antioxidants by directly supporting FSP1 stability and activity, thereby mitigating phospholipid peroxidation. Thus, we uncovered a direct role of vitamin B2 in maintaining membrane integrity and supporting membrane tolerance to lipid peroxidation and ferroptosis resistance. Our findings provide a rational strategy to modulate the FSP1-antioxidant recycling pathway, with potential implications for treating cancer and other diseases where ferroptosis plays a pivotal role.
HostingRepository	PRIDE
AnnounceDate	2025-10-31
AnnouncementXML	Submission_2025-10-31_11:48:25.802.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dominic Helm
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-21 01:34:16	ID requested
⏵ 1	2025-10-31 11:48:26	announced

Dataset with its publication pending

submitter keyword: Riboflavin,Ferroptosis, FSP1, Cell death, Vitamin B2

José Pedro Friedmann Angeli
contact affiliation	Rudolf Virchow Zentrum – University of Würzburg
contact email	pedro.angeli@uni-wuerzburg.de
lab head
Dominic Helm
contact affiliation	Proteomics Core Facility, German Cancer Research Center (DKFZ)
contact email	proteomicscore@dkfz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD061038
     1. Label: PRIDE project
     2. Name: Riboflavin metabolism shapes FSP1-driven ferroptosis resistance