Dynamic Cardiolipin Synthesis Is Required for CD8+ T Cell Immunity

Mauro Corrado, Joy Edwards-Hicks, Matteo Villa, Lea J Flachsmann, David E Sanin, Maaike Jacobs, Francesc Baixauli, Michal Stanczak, Eve Anderson, Mai Azuma, Andrea Quintana, Jonathan D Curtis, Thomas Clapes, Katarzyna M Grzes, Agnieszka M Kabat, Ryan Kyle, Annette E Patterson, Ramon Klein Geltink, Borko Amulic, Colin G StewardDouglas Strathdee, Eirini Trompouki, David O'Sullivan, Edward J Pearce, Erika L Pearce*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

29 Citations (Scopus)
78 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)981-995.e7
Number of pages23
JournalCell Metabolism
Issue number6
Publication statusPublished - 1 Dec 2020


  • cardiolipin
  • mitochodria
  • immunometabolism
  • PTPMT1
  • Tafazzin
  • Barth Syndrome
  • immune memory
  • CD8 T cells


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