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

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

Author information

1
Program in Immunobiology, Department of Medicine, University of Vermont, Burlington, Vermont, 05405 USA.
2
Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO 80045, USA.
3
Center for Cooperative Research in Biosciences (CIC bioGUNE), Derio 48160 Bizkaia, Spain.
4
Department of Chemistry, Center for Electro-Photo Behaviors in Advanced Molecular Systems, Pohang University of Science and Technology (POSTECH), Nam-Gu, Pohang, 790-784 Gyeongbuk, Republic of Korea.
5
Center on Aging and Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030 USA.
6
Center for Cooperative Research in Biosciences (CIC bioGUNE), Derio 48160 Bizkaia, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Bizkaia, Spain.
7
Program in Immunobiology, Department of Medicine, University of Vermont, Burlington, Vermont, 05405 USA. Electronic address: mrincon@uvm.edu.

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.

PMID:
27234056
PMCID:
PMC4917451
DOI:
10.1016/j.immuni.2016.02.018
[Indexed for MEDLINE]
Free PMC Article

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