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

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...

Full description

Saved in:
Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2016-06, Vol.44 (6), p.1299-1311
Main Authors: Champagne, Devin P., Hatle, Ketki M., Fortner, Karen A., D’Alessandro, Angelo, Thornton, Tina M., Yang, Rui, Torralba, Daniel, Tomás-Cortázar, Julen, Jun, Yong Woong, Ahn, Kyo Han, Hansen, Kirk C., Haynes, Laura, Anguita, Juan, Rincon, Mercedes
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Animals
CD8-Positive T-Lymphocytes - physiology
Cell growth
Cell Respiration
Cells, Cultured
Cytokines
Electron Transport Chain Complex Proteins - metabolism
Experiments
Flow cytometry
Gene expression
Glucose
Immunologic Memory
Infections
Influenza
Influenza virus
Interferon-gamma - metabolism
Lymphocyte Activation
Lymphocytes
Metabolism
Metabolome
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy
Mitochondria - metabolism
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Molecular Chaperones - genetics
Molecular Chaperones - metabolism
Orthomyxoviridae - immunology
Orthomyxoviridae Infections - immunology
Ovarian cancer
Oxidative Phosphorylation
Proteins
Respiration
Viral infections
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. •MCJ is a novel negative regulator of mitochondrial respiration in CD8+ T cells•Increased mitochondrial ATP in MCJ-deficient CD8+ T cells enhances cytokine secretion•MCJ adapts effector CD8+ T cell metabolism during the contraction phase•MCJ-deficient memory CD8+ T cells confer superior protection against influenza virus The endogenous molecular mechanisms controlling mitochondrial respiration in CD8+ T cells are not fully understood. In this issue of Immunity, Rincon and colleagues reveal that MCJ is a negative regulator of mitochondrial respiration in CD8+ T cells. Loss of MCJ enhances protective activity of memory CD8+ T cells against influenza virus.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2016.02.018