Cell
Volume 166, Issue 1, 30 June 2016, Pages 63-76
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Article
Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming

https://doi.org/10.1016/j.cell.2016.05.035Get rights and content
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Highlights

  • TM cells have fused mitochondria while TE cells have fissed mitochondria

  • Mitochondrial fusion protein Opa1 is required for TM cells and not TE cells

  • Enforcing fusion improves adoptive cellular immunotherapy against tumors

  • Cristae remodeling via fusion/fission signals metabolic adaptations in T cells

Summary

Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, by altering cristae morphology, fusion in TM cells configures electron transport chain (ETC) complex associations favoring oxidative phosphorylation (OXPHOS) and FAO, while fission in TE cells leads to cristae expansion, reducing ETC efficiency and promoting aerobic glycolysis. Thus, mitochondrial remodeling is a signaling mechanism that instructs T cell metabolic programming.

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