Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Corrado, M; Edwards-Hicks, J; Villa, M; Flachsmann, LJ; Sanin, DE; Jacobs, M; Baixauli, F; Stanczak, M; Anderson, E; Azuma, M; Quintana, A; Curtis, JD; Clapes, T; Grzes, KM; Kabat, AM; Kyle, R; Patterson, AE; Geltink, RK; Amulic, B; Steward, CG; Strathdee, D; Trompouki, E; O'Sullivan, D; Pearce, EJ; Pearce, EL.
Dynamic Cardiolipin Synthesis Is Required for CD8(+) T Cell Immunity
CELL METAB. 2020; 32(6):
Doi: 10.1016/j.cmet.2020.11.003
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- Co-authors Med Uni Graz
- Villa Matteo
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- 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 of a mitochondrial is crucial for CD8(+) T cell