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Compensatory electron transfer from the ubiquinol pool circumvents cytochrome c oxidase deficiency and restores effector and memory T cell function

ABSTRACT: The ultimate goal of immunometabolism is to modulate metabolic pathways to enhance immunity. Here, we investigate the potential of an alternative oxidase (AOX) to counteract cytochrome c oxidase (COX) deficiency in T cells. COX is vital for oxidative phosphorylation (OXPHOS), and its deficiency leads to redox imbalances, impaired metabolism, reactive oxygen species (ROS), and apoptosis, resulting in T cell immunodeficiency. We introduced an AOX into COX-deficient T cells, which revealed a normalization of genes involved in redox balance, apoptosis, and metabolic pathways. Mitochondrial function, glycolysis and TCA cycle function were also restored. AOX-enhanced T cells showed improved activation, proliferation, differentiation, and memory formation, resulting in better immune responses against viral challenges. These findings suggest that targeting the ubiquinol pool could be a promising therapeutic strategy for enhancing T cell function in conditions characterized by COX dysfunction and compromised immune responses.

ORGANISM(S): Mus musculus

PROVIDER: GSE269797 | GEO | 2024/10/02

REPOSITORIES: GEO

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Complexome profiling of heart mitochondria from mouse expressing alternative oxidase

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