PXD047622

PXD047622 is an original dataset announced via ProteomeXchange.

Title	NINJ1 induces plasma membrane rupture and DAMP release during ferroptosis
Description	Ferroptosis is a regulated form of necrotic cell death caused by an iron-dependent accumulation of oxidized phospholipids in cellular membranes, which culminates in plasma membrane rupture (PMR) and cell lysis. PMR is also a hallmark of other types of programmed necrosis, such as pyroptosis and necroptosis, where it is initiated by dedicated pore-forming cell death executors. Yet, whether ferroptosis-associated PMR is actively executed by a protein or driven by osmotic pressure remains unknown. Here, we investigated the role of ninjurin-1 (NINJ1), the recently identified executor of pyroptosis-associated PMR, in ferroptosis. We report that during ferroptosis NINJ1 oligomerizes and that Ninj1-deficiency protects macrophages and fibroblasts from ferroptosis-associated PMR. Mechanistically, we find that NINJ1 is dispensable for the early steps of ferroptosis, such as lipid peroxidation, channel-mediated calcium influx and cell swelling. By contrast, NINJ1 is required for early loss of plasma membrane integrity, an event that precedes complete PMR. Furthermore, NINJ1 mediates the release of cytosolic proteins and danger-associated molecular patterns (DAMPs) from ferroptotic cells, suggesting that targeting NINJ1 could be a therapeutic option to reduce ferroptosis-associated inflammation.
HostingRepository	PRIDE
AnnounceDate	2024-02-15
AnnouncementXML	Submission_2024-02-15_01:15:44.380.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Manfredo Quadroni
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-07 09:22:37	ID requested
⏵ 1	2024-02-15 01:15:44	announced

10.1038/S44318-024-00055-Y;

submitter keyword: DAMP release, SILAC,Ferroptosis, Ninj1

Petr Broz
contact affiliation	Department of Immunobiology, University of Lausanne, Switzerland
contact email	petr.broz@unil.ch
lab head
Manfredo Quadroni
contact affiliation	University of Lausanne
contact email	manfredo.quadroni@unil.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047622
     1. Label: PRIDE project
     2. Name: NINJ1 induces plasma membrane rupture and DAMP release during ferroptosis