PXD015727-1

PXD015727 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-07 02:38:17	ID requested
⏵ 1	2019-11-06 02:28:39	announced

Dataset with its publication pending

submitter keyword: Mouse, nLC-MS/MS, Orbitrap, Proteome Discoverer, Scaffold, Label-free

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

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PRIDE project URI

• PRIDE
  1. PXD015727
     1. Label: PRIDE project
     2. Name: Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage