Fine-Tuning of CD8(+) T Cell Mitochondrial Metabolism by the Respiratory Chain Repressor MCJ Dictates Protection to Influenza Virus

Immunity. 2016 Jun 21;44(6):1299-311. doi: 10.1016/j.immuni.2016.02.018. Epub 2016 May 24.


Mitochondrial respiration is regulated in CD8(+) T cells during the transition from naive to effector and memory cells, but mechanisms controlling this process have not been defined. Here we show that MCJ (methylation-controlled J protein) acted as an endogenous break for mitochondrial respiration in CD8(+) T cells by interfering with the formation of electron transport chain respiratory supercomplexes. Metabolic profiling revealed enhanced mitochondrial metabolism in MCJ-deficient CD8(+) T cells. Increased oxidative phosphorylation and subcellular ATP accumulation caused by MCJ deficiency selectively increased the secretion, but not expression, of interferon-γ. MCJ also adapted effector CD8(+) T cell metabolism during the contraction phase. Consequently, memory CD8(+) T cells lacking MCJ provided superior protection against influenza virus infection. Thus, MCJ offers a mechanism for fine-tuning CD8(+) T cell mitochondrial metabolism as an alternative to modulating mitochondrial mass, an energetically expensive process. MCJ could be a therapeutic target to enhance CD8(+) T cell responses.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Respiration
  • Cells, Cultured
  • Electron Transport Chain Complex Proteins / metabolism*
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Lymphocyte Activation
  • Metabolome
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Orthomyxoviridae / immunology*
  • Orthomyxoviridae Infections / immunology*
  • Oxidative Phosphorylation


  • Electron Transport Chain Complex Proteins
  • Mcj protein, mouse
  • Mitochondrial Proteins
  • Molecular Chaperones
  • Interferon-gamma
  • Adenosine Triphosphate