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学術論文

Dynamic Cardiolipin Synthesis Is Required for CD8+ T Cell Immunity

MPS-Authors
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Corrado,  Mauro
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Edwards-Hicks,  Joy
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Villa,  Matteo
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Flachsmann,  Lea J
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Sanin,  Pena David Estaban
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Jacobs,  Maaike
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Baixauli Celda,  Francesc
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Stanczak,  Michal
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Azuma,  Mai
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Quintana,  Andrea
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Jonathan,  Curtis
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Clapes,  Thomas
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Grzes,  Katarzyna
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Kabat,  Agnieska
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Ryan,  Kyle
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Annette,  Elizabeth Patterson
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Klein-Geltink,  Ramon
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Trompouki,  Eirini
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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O'Sullivan,  David
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce,  Edward Jonathen
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce,  Erika Laine
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource

https://www.sciencedirect.com/science/article/pii/S1550413120305982?via%3Dihub
(出版社版)

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引用

Corrado, M., Edwards-Hicks, J., Villa, M., Flachsmann, L. J., Sanin, P. D. E., Jacobs, M., Baixauli Celda, F., Stanczak, M., Anderson, E., Azuma, M., Quintana, A., Jonathan, C., Clapes, T., Grzes, K., Kabat, A., Ryan, K., Annette, E. P., Klein-Geltink, R., Amulic, B., Steward, C. G., Strathdee, D., Trompouki, E., O'Sullivan, D., Pearce, E. J., & Pearce, E. L. (2020). Dynamic Cardiolipin Synthesis Is Required for CD8+ T Cell Immunity. Cell Metabolism, 32, 981-995. doi:10.1016/j.cmet.2020.11.003.


引用: https://hdl.handle.net/21.11116/0000-0007-84C3-7
要旨
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.