Dynamic Cardiolipin Synthesis Is Required for CD8+ T Cell Immunity
| Autor: | Eirini Trompouki, Michal A. Stanczak, Mai Azuma, Maaike Jacobs, Andrea Quintana, Katarzyna M. Grzes, Agnieszka M. Kabat, Thomas Clapes, Eve Anderson, Francesc Baixauli, Ramon I. Klein Geltink, Jonathan D. Curtis, Joy Edwards-Hicks, Lea J. Flachsmann, Edward J. Pearce, Colin G. Steward, Annette E. Patterson, Ryan Kyle, Matteo Villa, David E. Sanin, David O’Sullivan, Erika L. Pearce, Mauro Corrado, Borko Amulic, Douglas Strathdee |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cardiolipins Physiology immunometabolism Cell PTPMT1 Tafazzin CD8 T cells CD8-Positive T-Lymphocytes Mitochondrion immune memory Article Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine mitochodria medicine Cardiolipin Animals Humans Cytotoxic T cell Molecular Biology Cells Cultured Mice Knockout biology PTEN Phosphohydrolase Barth syndrome Cell Biology medicine.disease Mitochondria Cell biology Mice Inbred C57BL De novo synthesis 030104 developmental biology medicine.anatomical_structure chemistry Barth Syndrome biology.protein Female lipids (amino acids peptides and proteins) cardiolipin Acyltransferases 030217 neurology & neurosurgery CD8 |
| Zdroj: | Cell Metabolism Corrado, M, Edwards-Hicks, J, Villa, M, Flachsmann, L J, Sanin, D E, Jacobs, M, Baixauli, F, Stanczak, M, Anderson, E, Azuma, M, Quintana, A, Curtis, J D, Clapes, T, Grzes, K M, Kabat, A M, Kyle, R, Patterson, A E, Geltink, R K, 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, vol. 32, no. 6, pp. 981-995.e7 . https://doi.org/10.1016/j.cmet.2020.11.003 |
| ISSN: | 1550-4131 |
| Popis: | Summary 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. Graphical Abstract Highlights • Cardiolipin is essential for in vivo and in vitro CD8+ T cell responses • Active cardiolipin synthesis and remodeling occurs during T cell differentiation • Cardiolipin synthesis supports CD8+ TM cell development, metabolism, and function • T cell defects are evident in TAZ KO mice and in Barth syndrome patients Corrado et al. show that the mitochondrial membrane-specific lipid cardiolipin is required for the metabolic plasticity that is essential for effective CD8+ T cell function. Cardiolipin-deficient CD8+ T cells fail to respond to pathogens and are not able to adapt to nutrient stress. |
| Databáze: | OpenAIRE |
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