Academic Journal
The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate
| العنوان: | The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate |
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| المؤلفون: | Weisshaar, Nina, Ma, Sicong, Ming, Yanan, Madi, Alaa, Mieg, Alessa, Hering, Marvin, Zettl, Ferdinand, Mohr, Kerstin, Ten Bosch, Nora, Stichling, Diana, Buettner, Michael, Poschet, Gernot, Klinke, Glynis, Schulz, Michael, Kunze-Rohrbach, Nina, Kerber, Carolin, Klein, Isabel Madeleine, Wu, Jingxia, Wang, Xi, Cui, Guoliang |
| المصدر: | Nature Immunology ; volume 24, issue 11, page 1921-1932 ; ISSN 1529-2908 1529-2916 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | The malate shuttle is traditionally understood to maintain NAD + /NADH balance between the cytosol and mitochondria. Whether the malate shuttle has additional functions is unclear. Here we show that chronic viral infections induce CD8 + T cell expression of GOT1, a central enzyme in the malate shuttle. Got1 deficiency decreased the NAD + /NADH ratio and limited antiviral CD8 + T cell responses to chronic infection; however, increasing the NAD + /NADH ratio did not restore T cell responses. Got1 deficiency reduced the production of the ammonia scavenger 2-ketoglutarate (2-KG) from glutaminolysis and led to a toxic accumulation of ammonia in CD8 + T cells. Supplementation with 2-KG assimilated and detoxified ammonia in Got1 -deficient T cells and restored antiviral responses. These data indicate that the major function of the malate shuttle in CD8 + T cells is not to maintain the NAD + /NADH balance but rather to detoxify ammonia and enable sustainable ammonia-neutral glutamine catabolism in CD8 + T cells during chronic infection. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41590-023-01636-5 |
| الاتاحة: | http://dx.doi.org/10.1038/s41590-023-01636-5 https://www.nature.com/articles/s41590-023-01636-5.pdf https://www.nature.com/articles/s41590-023-01636-5 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.3EDE0A41 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41590-023-01636-5 |
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