PXD055084-1

PXD055084 is an original dataset announced via ProteomeXchange.

Title	Glutamate utilization fuels rapid production of mitochondrial ROS in dendritic cells and drives systemic inflammation following Francisella infection
Description	Dendritic cells (DCs) hijacked by intracellular bacteria contribute to pathogen dissemination and immunopathology. How bacteria achieve DC subversion remains largely unknown. Here, we describe the mechanism used by intracellular pathogen Francisella tularensis exploiting host mitochondria. Shortly after internalization, Francisella associates with DC mitochondria which leads to rapid repurposing of their oxidative metabolism for production of mitochondrial reactive oxygen species (mtROS). Mitochondrial metabolic rewiring is orchestrated by intra-mitochondrial signaling mediated by protein acetylation and involves switching to glutamate as the primary substrate for DC tricarboxylic acid cycle. Rather than killing bacterium, glutamate-fueled mtROS production triggers p38-dependent proinflammatory gene expression and blocking of glutamate utilization prevents DC activation, bacterial dissemination, and alleviates immunopathology of severe infection. Our findings underscore the importance of metabolic plasticity in anti-bacterial DC response and open up new possibilities for therapies targeting host metabolism.
HostingRepository	PRIDE
AnnounceDate	2025-07-21
AnnouncementXML	Submission_2025-07-21_13:37:41.173.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ivo Fabrik
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	6x(13)C; acetylated residue; monohydroxylated residue; 6x(13)C labeled L-arginine; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-22 09:24:17	ID requested
⏵ 1	2025-07-21 13:37:41	announced

Dataset with its publication pending

submitter keyword: acetylome, Francisella tularensis,Dendritic cells, TCA cycle, reactive oxygen species, glutamate, mitochondria

Ivo Fabrik
contact affiliation	Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czechia
contact email	ivo.fabrik@fnhk.cz
lab head
Ivo Fabrik
contact affiliation	Biomedical Research Center, University Hospital Hradec Kralove
contact email	ivo.fabrik@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055084
     1. Label: PRIDE project
     2. Name: Glutamate utilization fuels rapid production of mitochondrial ROS in dendritic cells and drives systemic inflammation following Francisella infection