PXD010628-2

PXD010628 is an original dataset announced via ProteomeXchange.

Title	Nitric oxide modulates metabolic remodelling and immunometabolism in inflammatory murine macrophages
Description	Classical stimulation of macrophages (MLPS/IFNγ) elicits the expression of inducible nitric oxide synthase (iNOS), generating large amounts of nitric oxide (NO) and inhibiting respiration. Consequent upregulation of glycolysis and a disrupted tricarboxylic acid (TCA) cycle underpin this switch to a pro-inflammatory phenotype. Here we show that the NOS cofactor tetrahydrobiopterin (BH4) modulates key aspects of metabolic remodelling in activated bone-marrow-derived macrophages (BMDMs) via NO production. Using two complementary mouse models that each lack the capacity for inducible NO generation, through different mechanisms, we reveal that NO regulates macrophage respiratory function via changes in the abundance of critical N-module subunits in Complex I, by HIF1α-mediated glycolytic remodelling, and by modulating levels of the critical TCA cycle metabolites, and inflammatory mediators, citrate, succinate, and itaconate. Taken together, our findings reveal new critical roles for iNOS-derived NO that are required for metabolic remodelling and cytokine production in macrophage inflammatory responses.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:47:11.407.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simon Davis
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-31 05:25:47	ID requested
1	2019-05-31 03:27:19	announced
⏵ 2	2024-10-22 04:47:11	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: Mus musculus, Orbitrap Fusion Lumos

Roman Fischer
contact affiliation	Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Simon Davis
contact affiliation	University of Oxford
contact email	simon.davis2@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010628
     1. Label: PRIDE project
     2. Name: Nitric oxide modulates metabolic remodelling and immunometabolism in inflammatory murine macrophages