
==== Front
Res Sq
ResearchSquare
Research Square
2693-5015
American Journal Experts

10.21203/rs.3.rs-4875322/v1
10.21203/rs.3.rs-4875322
preprint
1
Article
Cytochrome c oxidase dependent respiration is essential for T cell activation, proliferation and memory formation
McGuire Peter https://orcid.org/0000-0001-5601-3044

Tarasenko Tatiana
Warren Emily https://orcid.org/0000-0002-3561-3478

Fuchs Amanda https://orcid.org/0000-0002-7085-0727

Singh Bharati
Marin Jose
Szibor Marten
10 9 2024
rs.3.rs-4875322https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
https://www.researchsquare.com/article/rs-4875322/v1
nihpp-rs4875322v1.pdf
Abstract

AAlthough glycolysis has received considerable attention in activated T cells, the utility and requirement of cytochrome c oxidase (COX) mediated mitochondrial respiration (MR) in T cell activation and function remain incompletely understood. To address this, we re-introduced MR via an alternative oxidase (AOX) from Ciona intestinalis into COX deficient T cells. Our findings reveal that MR serves as a critical safety valve for metabolic reprogramming during T cell activation, managing electron pressure and maintaining cellular redox balance. AOX-mediated MR restored mitochondrial function, reduced oxidative stress, and enhanced ATP production. This resulted in the elimination of the secondary effects of COX dysfunction, such as apoptosis and metabolic perturbations in glycolysis and the tricarboxylic acid cycle, thereby supporting robust effector and memory T cell generation and function. Our results underscore the importance of maintaining COX integrity for overall cellular health and emphasize the pivotal role of MR in T cell cellular proliferation and differentiation.
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