Dynamic Cardiolipin Synthesis Is Required for CD8+ T Cell Immunity.
Cell Metab
; 32(6): 981-995.e7, 2020 12 01.
Article
em En
| MEDLINE
| ID: mdl-33264603
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aciltransferases
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Cardiolipinas
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Linfócitos T CD8-Positivos
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PTEN Fosfo-Hidrolase
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Síndrome de Barth
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Mitocôndrias
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cell Metab
Assunto da revista:
METABOLISMO
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha