PXD015727 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage |
Description | DNA damage and metabolic disorders are intimately linked with premature disease onset but the underlying mechanisms remain poorly understood. Here, we show that persistent DNA damage accumulation in tissue-infiltrating macrophages carrying an ERCC1-XPF DNA repair defect (Er1F/-) riggers Golgi dispersal, dilation of endoplasmic reticulum, autophagy and exosome biogenesis leading to the secretion of extracellular vesicles (EVs) in vivo and ex vivo. Macrophage-derived EVs accumulate in Er1F/- animal sera and are secreted in macrophage media after DNA damage. The Er1F/- EV cargo is taken up by recipient cells leading to an increase in insulin-independent glucose transporter levels, enhanced cellular glucose uptake, higher cellular oxygen consumption rate and greater tolerance to glucose challenge in mice. We find that high glucose in EV-targeted cells triggers pro-inflammatory stimuli via mTOR activation. This, in turn, establishes chronic inflammation and tissue pathology in mice with important ramifications for DNA repair-deficient, progeroid syndromes and aging. |
HostingRepository | PRIDE |
AnnounceDate | 2019-11-06 |
AnnouncementXML | Submission_2019-11-06_02:28:38.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD015727 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Michalis Aivaliotis |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | Oxidation; Acetyl; Carbamidomethyl |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-10-07 02:38:17 | ID requested | |
⏵ 1 | 2019-11-06 02:28:39 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Mouse, nLC-MS/MS, Orbitrap, Proteome Discoverer, Scaffold, Label-free |
Contact List
Michalis Aivaliotis |
contact affiliation | Director of Proteomics Facility at IMBB (ProFI) |
contact email | aivaliot@imbb.forth.gr |
lab head | |
Michalis Aivaliotis |
contact affiliation | IMBB-FORTH/AUTH |
contact email | aivaliot@imbb.forth.gr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD015727
- Label: PRIDE project
- Name: Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage