| Autor: |
Lisci M; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY, UK., Barton PR; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY, UK., Randzavola LO; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY, UK., Ma CY; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY, UK., Marchingo JM; Cell Signalling and Immunology Division, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK., Cantrell DA; Cell Signalling and Immunology Division, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK., Paupe V; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY, UK., Prudent J; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY, UK., Stinchcombe JC; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY, UK., Griffiths GM; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY, UK. |
| Abstrakt: |
T cell receptor activation of naïve CD8 + T lymphocytes initiates their maturation into effector cytotoxic T lymphocytes (CTLs), which can kill cancer and virally infected cells. Although CTLs show an increased reliance on glycolysis upon acquisition of effector function, we found an essential requirement for mitochondria in target cell–killing. Acute mitochondrial depletion in USP30 (ubiquitin carboxyl-terminal hydrolase 30)–deficient CTLs markedly diminished killing capacity, although motility, signaling, and secretion were all intact. Unexpectedly, the mitochondrial requirement was linked to mitochondrial translation, inhibition of which impaired CTL killing. Impaired mitochondrial translation triggered attenuated cytosolic translation, precluded replenishment of secreted killing effectors, and reduced the capacity of CTLs to carry out sustained killing. Thus, mitochondria emerge as a previously unappreciated homeostatic regulator of protein translation required for serial CTL killing. |
