Work

Cytochrome c oxidase dependent respiration is essential for T cell activation, proliferation and memory formation

Year: 2025

Type: article

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.

Source: Nature Communications

DOI: 10.1038/s41467-025-65910-w