PXD012405 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Environmental Arginine Controls Multinuclear Giant Cell Metabolism and Formation |
Description | Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. Formation of MGCs is energy intensive to enforce membrane fusion and cytoplasmic expansion. Here we used receptor activator of nuclear factor kappa-Β ligand (RANKL) induced osteoclastogenesis to model MGC formation. We found amino acid (AA) scarcity controls MGC formation and reveal specific requirements for extracellular arginine in RANKL cellular programming. Indeed, systemic arginine restriction improved outcome in multiple murine arthritis models, by inducing preosteoclast metabolic quiescence, associated with a dysregulated tricarboxylic acid (TCA) cycle, and diverted metabolic fluxes from central metabolic pathways independent of mTORC1 activity or global transcriptional and translational inhibition. A conserved metabolic mechanism occurred in IL-4 induced MGCs. Strikingly, we demonstrate that restriction of multiple AAs triggered metabolic adaptation and blocked MGC formation and each was rescued by their downstream metabolites. These data establish how environmental nutrients control the metabolic fate of polykaryons and suggest metabolic ways to manipulate MGC-associated pathologies and bone remodeling. |
HostingRepository | PRIDE |
AnnounceDate | 2019-12-18 |
AnnouncementXML | Submission_2019-12-18_07:08:18.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Mario Oroshi |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-01-17 02:28:24 | ID requested | |
1 | 2019-12-17 07:20:20 | announced | |
⏵ 2 | 2019-12-18 07:08:19 | announced | 2019-12-18: Updated project metadata. |
3 | 2020-01-29 06:29:58 | announced | 2019-12-18: Updated project metadata.
2020-01-29: Updated publication reference for PubMed record(s): 31969567. |
Publication List
Dataset with its publication pending |
Keyword List
curator keyword: Biomedical |
submitter keyword: Arginine, Preosteoclasts, RANKL, LC-MS |
Contact List
Gernot Schabbauer |
contact affiliation | Institute for Vascular Biology, Center for Physiology and Pharmacology, Medical University Vienna, Vienna, Austria |
contact email | gernot.schabbauer@meduniwien.ac.at |
lab head | |
Mario Oroshi |
contact affiliation | Proteomics |
contact email | oroshi@biochem.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD012405
- Label: PRIDE project
- Name: Environmental Arginine Controls Multinuclear Giant Cell Metabolism and Formation