Mitochondrial translation is required for sustained killing by cytotoxic T cells

• DOI: 10.1126/science.abe9977
• Publication Date: 2021-10-15T03:03:53Z
• Authors: Miriam Lisci; Philippa R. Barton; Lyra O. Randzavola; Claire Y. Ma; Julia M. Marchingo; Doreen A. Cantrell; Vincent Paupe; Julien Prudent; Jane C. Stinchcombe; Gillian M. Griffiths
• Keywords: Cytotoxicity, Immunologic; Mice, Knockout; 0301 basic medicine; 610; 612; Mitochondria; 12. Responsible consumption; 3. Good health; Mice, Inbred C57BL; Mitochondrial Proteins; Mice; 03 medical and health sciences; name=General; Adenosine Triphosphate; Cell Movement; Protein Biosynthesis; /dk/atira/pure/subjectarea/asjc/1000; Animals; Thiolester Hydrolases; Cells, Cultured; T-Lymphocytes, Cytotoxic

Mitochondria drive CTLs’ killer instinct

Cytotoxic T lymphocytes (CTLs) can terminate both virally infected cells and cancer cells by secreting cytolytic proteins such as perforin and granzyme B. CTLs are particularly effective because they can sequentially kill multiple targets in a process called serial killing. Lisci et al . have identified mitochondria as important regulators of CTL killing. Mice lacking the deubiquitinase USP30 have CTLs acutely depleted of mitochondria, and these cells have reduced killing ability but normal motility, signaling, and secretion. Surprisingly, the mitochondria’s metabolic functions were not required for this process. Rather, mitochondrial translation proved indispensable for CTL cytolytic protein synthesis and sustained CTL killing. —STS