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@ARTICLE{Weisshaar:284615,
      author       = {N. Weisshaar$^*$ and S. Ma and Y. Ming and A. A. M.
                      Madi$^*$ and A. Mieg$^*$ and M. Hering$^*$ and F. Zettl$^*$
                      and K. Mohr$^*$ and N. ten Bosch$^*$ and D. Stichling$^*$
                      and M. Buettner and G. Poschet and G. Klinke and M. Schulz
                      and N. Kunze-Rohrbach and C. Kerber and I. M. Klein and J.
                      Wu and X. Wang and G. Cui$^*$},
      title        = {{T}he malate shuttle detoxifies ammonia in exhausted {T}
                      cells by producing 2-ketoglutarate.},
      journal      = {Nature immunology},
      volume       = {24},
      number       = {11},
      issn         = {1529-2908},
      address      = {London},
      publisher    = {Springer Nature Limited},
      reportid     = {DKFZ-2023-02034},
      pages        = {1921-1932},
      year         = {2023},
      note         = {2023 Nov;24(11):1921-1932 / #EA:D192#LA:D192# / HI-TRON},
      abstract     = {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.},
      cin          = {D192},
      ddc          = {610},
      cid          = {I:(DE-He78)D192-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37813964},
      doi          = {10.1038/s41590-023-01636-5},
      url          = {https://inrepo02.dkfz.de/record/284615},
}