Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming

Cell. 2016 Jun 30;166(1):63-76. doi: 10.1016/j.cell.2016.05.035. Epub 2016 Jun 9.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Electron Transport
  • Fatty Acids / metabolism
  • GTP Phosphohydrolases / metabolism
  • Glycolysis
  • Humans
  • Immunologic Memory
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Dynamics*
  • Oxidation-Reduction
  • Signal Transduction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*


  • Fatty Acids
  • GTP Phosphohydrolases
  • Opa1 protein, mouse