PXD027737 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Nrf2 is a central regulator of the metabolic landscape in macrophages and finetunes their inflammatory response |
Description | To overcome oxidative, inflammatory, and metabolic stress, cells have evolved networks of cytoprotective proteins controlled by transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) and its main negative regulator the Kelch-like ECH associated protein 1 (Keap1). Here, we used high-resolution mass-spectrometry to characterize the proteomes of macrophages with altered Nrf2 status. Our analysis revealed significant differences among the genotypes in cellular metabolism and redox homeostasis, which we validated with Seahorse flux and metabolomics, as well as in anti-viral immune pathways, translational regulation and mitosis. Nrf2 disruption significantly affected the proteome following lipopolysaccharide (LPS) stimulation, with alterations in redox, carbohydrate and lipid metabolism, and innate immunity predominantly. Of note, LPS stimulation was found to promote mitochondrial fusion in a process that was dependent on Nrf2. The Keap1 inhibitor, 4-octyl itaconate (4-OI), a derivative of the mitochondrial immunometabolite itaconate, remodeled the inflammatory macrophage proteome, increasing redox and suppressing anti-viral immune effectors in a Nrf2-dependent manner. These data suggest that Nrf2 activation facilitates metabolic reprogramming, mitochondrial adaptation, and finetunes the innate immune response in macrophages. |
HostingRepository | PRIDE |
AnnounceDate | 2021-08-13 |
AnnouncementXML | Submission_2021-08-13_08:25:31.766.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Alejandro Brenes |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | acetylated residue; deamidated residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-08-05 08:59:41 | ID requested | |
⏵ 1 | 2021-08-13 08:25:32 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: BMDM, TMT, NRF2, KEAP1, murine, mitochondria |
Contact List
Doreen A. Cantrell |
contact affiliation | Cell Signalling & Immunology, School of Life Sciences, University of Dundee |
contact email | d.a.cantrell@dundee.ac.uk |
lab head | |
Alejandro Brenes |
contact affiliation | University of Dundee |
contact email | ajbrenesmurillo@dundee.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD027737
- Label: PRIDE project
- Name: Nrf2 is a central regulator of the metabolic landscape in macrophages and finetunes their inflammatory response