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Journal Article

Dynamic Cardiolipin Synthesis Is Required for CD8+ T Cell Immunity

MPS-Authors
/persons/resource/persons201354

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;

/persons/resource/persons204375

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;

/persons/resource/persons201442

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;

/persons/resource/persons201355

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

/persons/resource/persons253258

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

/persons/resource/persons204377

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

/persons/resource/persons204379

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

/persons/resource/persons201361

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

/persons/resource/persons201441

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

/persons/resource/persons201360

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

/persons/resource/persons241707

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

/persons/resource/persons201374

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

/persons/resource/persons201435

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

/persons/resource/persons201431

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
(Publisher version)

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Citation

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.


Cite as: https://hdl.handle.net/21.11116/0000-0007-84C3-7
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.