Published on Tue Apr 09 2019

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

Devin P Champagne, Ketki M Hatle, Karen A Fortner, Angelo D'Alessandro, Tina M Thornton, Rui Yang, Daniel Torralba, Julen Tomás-Cortázar, Yong Woong Jun, Kyo Han Ahn, Kirk C Hansen, Laura Haynes, Juan Anguita, Mercedes Rincon

Mitochondrial respiration is regulated in CD8(+) T cells during the transition from naive to effector and memory cells. MCJ (methylation-controlled J protein) acted as an endogenous break for mitochondrial respiration.

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Abstract

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.