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

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2016 May 29

PMID 27234056

Citations 37

Authors

Devin P Champagne

Ketki M Hatle

Karen A Fortner

Angelo DAlessandro

Tina M Thornton

Rui Yang

Daniel Torralba

Julen Tomas-Cortazar

Yong Woong Jun

Kyo Han Ahn

Kirk C Hansen

Laura Haynes

Juan Anguita

Mercedes Rincon

Affiliations

Soon will be listed here.

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.

Citing Articles

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