PXD060723-1

PXD060723 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial damage drives T-cell immunometabolic paralysis after major surgery
Description	Cytotoxic T cell (CTL) dysfunction is a key feature of immune paralysis following major surgery, significantly increasing the risk of severe nosocomial infections and contributing to elevated mortality in critically ill patients. The pathomechanisms of CTL dysfunction remain unclear. We report that reactive oxygen species (ROS) release by Myeloid-Derived Suppressor Cells, which transiently and unexpectedly emerge after major surgery, drives perioperative CTL immunoparalysis. This ROS release causes a critical accumulation of ROS within CTL, overwhelming their antioxidative defenses and severely compromising mitochondrial membrane potential. Consequently, oxidative phosphorylation is impaired, and CTL effector functions are inhibited. Additionally, stress-induced mitochondrial hyperfusion occurs, which disrupts fission-dependent mitochondrial translocation to the immunological synapse, exacerbating the bioenergetic failure. These processes result in substantial mitochondrial dysfunction, which could be partially reversed by treatment with the mitochondria-targeting antioxidant MitoTempo. Stabilizing mitochondrial function could serve as a promising clinical strategy for preventing and treating perioperative immune dysfunction.
HostingRepository	PRIDE
AnnounceDate	2025-12-09
AnnouncementXML	Submission_2025-12-09_03:47:48.874.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Teresa Barth
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-12 06:29:52	ID requested
⏵ 1	2025-12-09 03:47:49	announced

Hirschberger S, M, ü, ller MB, Mascolo H, Seitz M, Nibler S, Effinger D, Lu K, B, ü, ch J, Bender M, Kammerer T, Peter, ß S, Kleigrewe K, Abele M, Barth T, Kushnir O, Imhof A, Dietzel S, Wegener B, Sowa R, Vogel F, Lamm P, Tomasi R, Unger K, Sperandio M, Kilger E, Kreth S, H, ü, bner M, Mitochondrial damage drives T-cell immunometabolic paralysis after major surgery. EMBO Mol Med, 17(12):3329-3354(2025) [pubmed]

10.1038/s44321-025-00324-1;

submitter keyword: None

Max Huebner
contact affiliation	Walter Brendel Centre of Experimental Medicine, Research Unit Immune Function and Immune Metabolism, Ludwig-Maximilian-University (LMU) Munich, Germany Department of Anaesthesiology, LMU University Hospital, LMU Munich, Germany
contact email	Max.Huebner@med.uni-muenchen.de
lab head
Teresa Barth
contact affiliation	Biomedical Center Munich, Ludwig-Maximilians-Universitaet Munich
contact email	teresa.barth@bmc.med.lmu.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/12/PXD060723

PRIDE project URI

• PRIDE
  1. PXD060723
     1. Label: PRIDE project
     2. Name: Mitochondrial damage drives T-cell immunometabolic paralysis after major surgery