Dynamic cardiolipin synthesis is required for CD8+ T cell immunity

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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Cell Metabolism. - 32, 6 (2020) , 981-995, ISSN: 1550-4131

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2024
• Urheber: Corrado, Mauro ; Edwards-Hicks, Joy ; Villa, Matteo ; Flachsmann, Lea J. ; Sanin, David E. ; Jacobs, Maaike ; Baixauli, Francesc ; Stanczak, Michal ; Anderson, Eve ; Azuma, Mai ; Quintana, Andrea ; Curtis, Jonathan D. ; Clapes, Thomas ; Grzes, Katarzyna M. ; Kabat, Agnieszka M. ; Kyle, Ryan L. ; Patterson, Annette E. ; Klein Geltink, Ramon I. ; Amulic, Borko ; Steward, Colin G. ; Strathdee, Douglas ; Trompouki, Eirini ; O’Sullivan, David ; Pearce, Edward J. ; Pearce, Erika L.

Weitere Informationen

• DOI: 10.1016/j.cmet.2020.11.003
• URN: urn:nbn:de:bsz:25-freidok-2597367
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:22 MESZ