Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage
Identifieur interne : 000016 ( an2020/Analysis ); précédent : 000015; suivant : 000017Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage
Auteurs : Evi Goulielmaki ; Anna Ioannidou ; Maria Tsekrekou ; Kalliopi Stratigi ; Ioanna K. Poutakidou ; Katerina Gkirtzimanaki ; Michalis Aivaliotis ; Konstantinos Evangelou [Grèce] ; Pantelis Topalis ; Janine Altmüller [Allemagne] ; Vassilis G. Gorgoulis [Grèce] ; Georgia Chatzinikolaou ; George A. GarinisSource :
- Nature Communications [ 2041-1723 ] ; 2020.
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 (
Url:
DOI: 10.1038/s41467-019-13894-9
PubMed: 31896748
PubMed Central: 6940362
Affiliations:
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PMC:6940362Le document en format XML
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Garinis</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0635 685X</institution-id><institution-id institution-id-type="GRID">grid.4834.b</institution-id><institution>Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas,</institution></institution-wrap>GR70013 Heraklion, Crete Greece</nlm:aff><wicri:noCountry code="subfield">Crete Greece</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0576 3437</institution-id><institution-id institution-id-type="GRID">grid.8127.c</institution-id><institution>Department of Biology,</institution><institution>University of Crete,</institution></institution-wrap>Heraklion, Crete Greece</nlm:aff><wicri:noCountry code="subfield">Crete Greece</wicri:noCountry></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">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 (<italic>Er1</italic><sup>F/−</sup>) 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 <italic>Er1</italic><sup>F/−</sup> animal sera and are secreted in macrophage media after DNA damage. The <italic>Er1</italic><sup>F/−</sup> 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Harper, Jw" uniqKey="Harper J">JW Harper</name></author><author><name sortKey="Elledge, Sj" uniqKey="Elledge S">SJ Elledge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoeijmakers, Jh" uniqKey="Hoeijmakers J">JH Hoeijmakers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gregg, Sq" uniqKey="Gregg S">SQ Gregg</name></author><author><name sortKey="Robinson, Ar" uniqKey="Robinson A">AR Robinson</name></author><author><name sortKey="Niedernhofer, Lj" uniqKey="Niedernhofer L">LJ Niedernhofer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Apostolou, Z" uniqKey="Apostolou Z">Z Apostolou</name></author><author><name sortKey="Chatzinikolaou, G" uniqKey="Chatzinikolaou G">G Chatzinikolaou</name></author><author><name sortKey="Stratigi, K" uniqKey="Stratigi K">K Stratigi</name></author><author><name sortKey="Garinis, Ga" uniqKey="Garinis G">GA Garinis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kamileri, I" uniqKey="Kamileri I">I Kamileri</name></author><author><name sortKey="Karakasilioti, I" uniqKey="Karakasilioti I">I Karakasilioti</name></author><author><name sortKey="Garinis, Ga" uniqKey="Garinis G">GA Garinis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hanawalt, Pc" uniqKey="Hanawalt P">PC Hanawalt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marteijn, Ja" uniqKey="Marteijn J">JA Marteijn</name></author><author><name sortKey="Lans, H" uniqKey="Lans H">H Lans</name></author><author><name sortKey="Vermeulen, W" uniqKey="Vermeulen W">W Vermeulen</name></author><author><name sortKey="Hoeijmakers, Jh" uniqKey="Hoeijmakers J">JH Hoeijmakers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Digiovanna, Jj" uniqKey="Digiovanna J">JJ DiGiovanna</name></author><author><name sortKey="Kraemer, Kh" uniqKey="Kraemer K">KH Kraemer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kamileri, Irene" uniqKey="Kamileri I">Irene Kamileri</name></author><author><name sortKey="Karakasilioti, Ismene" uniqKey="Karakasilioti I">Ismene Karakasilioti</name></author><author><name sortKey="Garinis, George A" uniqKey="Garinis G">George A. 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Aebersold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nesvizhskii, Ai" uniqKey="Nesvizhskii A">AI Nesvizhskii</name></author><author><name sortKey="Keller, A" uniqKey="Keller A">A Keller</name></author><author><name sortKey="Kolker, E" uniqKey="Kolker E">E Kolker</name></author><author><name sortKey="Aebersold, R" uniqKey="Aebersold R">R Aebersold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Searle, Bc" uniqKey="Searle B">BC Searle</name></author><author><name sortKey="Turner, M" uniqKey="Turner M">M Turner</name></author><author><name sortKey="Nesvizhskii, Ai" uniqKey="Nesvizhskii A">AI Nesvizhskii</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Asara, Jm" uniqKey="Asara J">JM Asara</name></author><author><name sortKey="Christofk, Hr" uniqKey="Christofk H">HR Christofk</name></author><author><name sortKey="Freimark, Lm" uniqKey="Freimark L">LM Freimark</name></author><author><name sortKey="Cantley, Lc" uniqKey="Cantley L">LC Cantley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Szklarczyk, D" uniqKey="Szklarczyk D">D Szklarczyk</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Grèce</li></country><region><li>Attique (région)</li></region><settlement><li>Athènes</li></settlement></list><tree><noCountry><name sortKey="Aivaliotis, Michalis" sort="Aivaliotis, Michalis" uniqKey="Aivaliotis M" first="Michalis" last="Aivaliotis">Michalis Aivaliotis</name><name sortKey="Chatzinikolaou, Georgia" sort="Chatzinikolaou, Georgia" uniqKey="Chatzinikolaou G" first="Georgia" last="Chatzinikolaou">Georgia Chatzinikolaou</name><name sortKey="Garinis, George A" sort="Garinis, George A" uniqKey="Garinis G" first="George A." last="Garinis">George A. Garinis</name><name sortKey="Gkirtzimanaki, Katerina" sort="Gkirtzimanaki, Katerina" uniqKey="Gkirtzimanaki K" first="Katerina" last="Gkirtzimanaki">Katerina Gkirtzimanaki</name><name sortKey="Goulielmaki, Evi" sort="Goulielmaki, Evi" uniqKey="Goulielmaki E" first="Evi" last="Goulielmaki">Evi Goulielmaki</name><name sortKey="Ioannidou, Anna" sort="Ioannidou, Anna" uniqKey="Ioannidou A" first="Anna" last="Ioannidou">Anna Ioannidou</name><name sortKey="Poutakidou, Ioanna K" sort="Poutakidou, Ioanna K" uniqKey="Poutakidou I" first="Ioanna K." last="Poutakidou">Ioanna K. Poutakidou</name><name sortKey="Stratigi, Kalliopi" sort="Stratigi, Kalliopi" uniqKey="Stratigi K" first="Kalliopi" last="Stratigi">Kalliopi Stratigi</name><name sortKey="Topalis, Pantelis" sort="Topalis, Pantelis" uniqKey="Topalis P" first="Pantelis" last="Topalis">Pantelis Topalis</name><name sortKey="Tsekrekou, Maria" sort="Tsekrekou, Maria" uniqKey="Tsekrekou M" first="Maria" last="Tsekrekou">Maria Tsekrekou</name></noCountry><country name="Grèce"><noRegion><name sortKey="Evangelou, Konstantinos" sort="Evangelou, Konstantinos" uniqKey="Evangelou K" first="Konstantinos" last="Evangelou">Konstantinos Evangelou</name></noRegion><name sortKey="Gorgoulis, Vassilis G" sort="Gorgoulis, Vassilis G" uniqKey="Gorgoulis V" first="Vassilis G." last="Gorgoulis">Vassilis G. Gorgoulis</name><name sortKey="Gorgoulis, Vassilis G" sort="Gorgoulis, Vassilis G" uniqKey="Gorgoulis V" first="Vassilis G." last="Gorgoulis">Vassilis G. Gorgoulis</name></country><country name="Allemagne"><noRegion><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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