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  Dynamic Cardiolipin Synthesis Is Required for CD8+ T Cell Immunity

Corrado, M., Edwards-Hicks, J., Villa, M., Flachsmann, L. J., Sanin, P. D. E., Jacobs, M., et al. (2020). Dynamic Cardiolipin Synthesis Is Required for CD8+ T Cell Immunity. Cell Metabolism, 32, 981-995. doi:10.1016/j.cmet.2020.11.003.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-84C3-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-AB02-6
Genre: Journal Article

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Corrado et al. 2020.pdf (Publisher version), 4MB
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2020
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 Creators:
Corrado, Mauro1, Author              
Edwards-Hicks, Joy1, Author
Villa, Matteo1, Author              
Flachsmann, Lea J1, Author
Sanin, Pena David Estaban1, Author              
Jacobs, Maaike1, Author
Baixauli Celda, Francesc1, Author              
Stanczak, Michal1, Author
Anderson, Eve2, Author
Azuma, Mai1, Author
Quintana, Andrea1, Author
Jonathan, Curtis1, Author              
Clapes, Thomas3, Author              
Grzes, Katarzyna1, Author              
Kabat, Agnieska1, Author              
Ryan, Kyle1, Author              
Annette, Elizabeth Patterson1, Author              
Klein-Geltink, Ramon1, Author              
Amulic, Borko2, Author
Steward, Colin G2, Author
Strathdee, Douglas2, AuthorTrompouki, Eirini3, Author              O'Sullivan, David1, Author              Pearce, Edward Jonathen1, Author              Pearce, Erika Laine1, Author               more..
Affiliations:
1Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_persistent22              
2External Organizations, ou_persistent22              
3Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_persistent22              

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Free keywords: cardiolipin, mitochodria, immunometabolism, PTPMT1, Tafazzin, Barth Syndrome, immune memory, CD8 T cells
 Abstract: Mitochondria constantly adapt to the metabolic needs of a cell. This mitochondrial plasticity is critical to T cells, which modulate metabolism depending on antigen-driven signals and environment. We show here that de novo synthesis of the mitochondrial membrane-specific lipid cardiolipin maintains CD8+ T cell function. T cells deficient for the cardiolipin-synthesizing enzyme PTPMT1 had reduced cardiolipin and responded poorly to antigen because basal cardiolipin levels were required for activation. However, neither de novo cardiolipin synthesis, nor its Tafazzin-dependent remodeling, was needed for T cell activation. In contrast, PTPMT1-dependent cardiolipin synthesis was vital when mitochondrial fitness was required, most notably during memory T cell differentiation or nutrient stress. We also found CD8+ T cell defects in a small cohort of patients with Barth syndrome, where TAFAZZIN is mutated, and in a Tafazzin-deficient mouse model. Thus, the dynamic regulation of a single mitochondrial lipid is crucial for CD8+ T cell immunity.

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Language(s): eng - English
 Dates: 2020-12-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.cmet.2020.11.003
 Degree: -

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Title: Cell Metabolism
  Other : Cell Metabolism
Source Genre: Journal
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Publ. Info: Cambridge, MA : Cell Press
Pages: - Volume / Issue: 32 Sequence Number: - Start / End Page: 981 - 995 Identifier: ISSN: 1550-4131
CoNE: https://pure.mpg.de/cone/journals/resource/111088195284928