NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8+ T Cells
Identifieur interne : 000607 ( Main/Exploration ); précédent : 000606; suivant : 000608NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8+ T Cells
Auteurs : Shubhranshu S. Gupta [États-Unis] ; Robert Sharp [États-Unis] ; Colby Hofferek [États-Unis] ; Le Kuai [États-Unis] ; Gerald W. Dorn [États-Unis] ; Jin Wang [États-Unis] ; Min Chen [États-Unis]Source :
- Cell reports [ 2211-1247 ] ; 2019.
Abstract
Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8+ T cells remain unclear. Here we show that deficiency in NIX-dependent mitophagy leads to metabolic defects in effector memory T cells. Deletion of NIX caused HIF1α accumulation and altered cellular metabolism from long-chain fatty acid to short/branched-chain fatty acid oxidation, thereby compromising ATP synthesis during effector memory formation. Preventing HIF1α accumulation restored long-chain fatty acid metabolism and effector memory formation in antigen-specific CD8+ T cells. Our study suggests that NIX-mediated mitophagy is critical for effector memory formation in T cells.
Url:
DOI: 10.1016/j.celrep.2019.10.032
PubMed: 31722203
PubMed Central: 6886713
Affiliations:
- États-Unis
- Missouri (État), État de New York
- Ithaca (New York), Saint-Louis (Missouri)
- Université Cornell, École de médecine (Université Washington de Saint-Louis)
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Dorn</name><affiliation wicri:level="4"><nlm:aff id="A3">Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName><placeName><settlement type="city">Saint-Louis (Missouri)</settlement><region type="state">Missouri (État)</region></placeName></affiliation></author><author><name sortKey="Wang, Jin" sort="Wang, Jin" uniqKey="Wang J" first="Jin" last="Wang">Jin Wang</name><affiliation wicri:level="1"><nlm:aff id="A4">Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX 77030</wicri:regionArea><wicri:noRegion>TX 77030</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A5">Department of Surgery, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Weill Cornell Medical College, Cornell University, New York, NY 10065</wicri:regionArea><orgName type="university">Université Cornell</orgName><placeName><settlement type="city">Ithaca (New York)</settlement><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Chen, Min" sort="Chen, Min" uniqKey="Chen M" first="Min" last="Chen">Min Chen</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea><wicri:noRegion>TX 77030</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea><wicri:noRegion>TX 77030</wicri:noRegion></affiliation><affiliation><nlm:aff id="A6">Lead Contact</nlm:aff></affiliation></author></analytic><series><title level="j">Cell reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>SUMMARY</title><p id="P3">Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8<sup>+</sup> T cells remain unclear. Here we show that deficiency in NIX-dependent mitophagy leads to metabolic defects in effector memory T cells. Deletion of NIX caused HIF1α accumulation and altered cellular metabolism from long-chain fatty acid to short/branched-chain fatty acid oxidation, thereby compromising ATP synthesis during effector memory formation. Preventing HIF1α accumulation restored long-chain fatty acid metabolism and effector memory formation in antigen-specific CD8<sup>+</sup> T cells. Our study suggests that NIX-mediated mitophagy is critical for effector memory formation in T cells.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Akondy, Rs" uniqKey="Akondy R">RS Akondy</name></author><author><name sortKey="Fitch, M" uniqKey="Fitch M">M Fitch</name></author><author><name sortKey="Edupuganti, S" uniqKey="Edupuganti S">S Edupuganti</name></author><author><name sortKey="Yang, S" uniqKey="Yang S">S Yang</name></author><author><name sortKey="Kissick, Ht" uniqKey="Kissick H">HT Kissick</name></author><author><name sortKey="Li, Kw" uniqKey="Li K">KW Li</name></author><author><name sortKey="Youngblood, Ba" uniqKey="Youngblood B">BA Youngblood</name></author><author><name sortKey="Abdelsamed, Ha" uniqKey="Abdelsamed H">HA Abdelsamed</name></author><author><name sortKey="Mcguire, Dj" uniqKey="Mcguire D">DJ McGuire</name></author><author><name sortKey="Cohen, Kw" uniqKey="Cohen K">KW 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Gupta</name></noRegion><name sortKey="Chen, Min" sort="Chen, Min" uniqKey="Chen M" first="Min" last="Chen">Min Chen</name><name sortKey="Chen, Min" sort="Chen, Min" uniqKey="Chen M" first="Min" last="Chen">Min Chen</name><name sortKey="Dorn, Gerald W" sort="Dorn, Gerald W" uniqKey="Dorn G" first="Gerald W." last="Dorn">Gerald W. Dorn</name><name sortKey="Gupta, Shubhranshu S" sort="Gupta, Shubhranshu S" uniqKey="Gupta S" first="Shubhranshu S." last="Gupta">Shubhranshu S. Gupta</name><name sortKey="Hofferek, Colby" sort="Hofferek, Colby" uniqKey="Hofferek C" first="Colby" last="Hofferek">Colby Hofferek</name><name sortKey="Kuai, Le" sort="Kuai, Le" uniqKey="Kuai L" first="Le" last="Kuai">Le Kuai</name><name sortKey="Sharp, Robert" sort="Sharp, Robert" uniqKey="Sharp R" first="Robert" last="Sharp">Robert Sharp</name><name sortKey="Wang, Jin" sort="Wang, Jin" uniqKey="Wang J" first="Jin" last="Wang">Jin Wang</name><name sortKey="Wang, Jin" sort="Wang, Jin" uniqKey="Wang J" first="Jin" last="Wang">Jin Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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