@article{3189101,
    title = "Tissue-infiltrating macrophages mediate an exosome-based metabolic
reprogramming upon DNA damage",
    author = "Goulielmaki, Evi and Ioannidou, Anna and Tsekrekou, Maria and Stratigi, and Kalliopi and Poutakidou, Ioanna K. and Gkirtzimanaki, Katerina and and Aivaliotis, Michalis and Evangelou, Konstantinos and Topalis, Pantelis and and Altmueller, Janine and Gorgoulis, Vassilis G. and Chatzinikolaou, and Georgia and Garinis, George A.",
    journal = "Nature Communications",
    year = "2020",
    volume = "11",
    number = "1",
    publisher = "Nature Publishing Group",
    issn = "2041-1723",
    doi = "10.1038/s41467-019-13894-9",
    abstract = "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
(Er1(F/-)) triggers 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 Er1(F/-) animal sera and are secreted in macrophage media
after DNA damage. The Er1(F/-) 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."
}