PXD061292

PXD061292 is an original dataset announced via ProteomeXchange.

Title	Pseudomonas aeruginosa manipulates a CNMT-TFR1 methylation pathway to drive macrophage ferroptosis via quorum sensing molecule PQS
Description	Pseudomonas aeruginosa employs quorum sensing (QS) small molecules such as Pseudomonas Quinolone Signal (PQS) to manipulate host cell death. Although PQS triggers several cell death modalities, its role in ferroptosis remains enigmatic. Here, we reported that PQS induces ferroptosis in macrophages through a previously unrecognized carnosine-N-methyltransferase (CNMT)-transferrin receptor 1 (TFR1) methylation pathway. Using thermal proteome profilingscreening, we identified CNMT as the direct intracellular receptor of PQS in macrophage. Mechanistically, PQS binding activates CNMT’s histidine methyltransferase activity, catalyzing H35 methylation on TFR1. This methylation modification increases TFR1 expressions, amplifying iron acquisition and lipid peroxidation for ferroptosis. Crucially, the PQS-CNMT-TFR1 axis is distinct from canonical bacterial pathogens that exploit host cell death pathways, revealing P. aeruginosa’s unique strategy to exploit host epigenetic machinery. Our findings redefine QS molecules as mediators of interkingdom signaling and position CNMT-TFR1 methylation as therapeutic targets aimed at blocking ferroptosis-driven immunopathology to mitigate P. aeruginosa virulence.
HostingRepository	iProX
AnnounceDate	2025-02-27
AnnouncementXML	Submission_2025-02-27_18:06:27.906.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fengming Li
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-27 18:06:15	ID requested
⏵ 1	2025-02-27 18:06:28	announced

Dataset with its publication pending

submitter keyword: PQS, RAW264.7, CNMT, ferroptosis

Chris Soon Heng Tan
contact affiliation	Southern University of Science and Technology
contact email	christan@sustech.edu.cn
lab head
Fengming Li
contact affiliation	Southern University of Science and Technology
contact email	12331077@mail.sustech.edu.cn
dataset submitter

iProX dataset URI