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September 10, 2025Open Access

Mitochondrial Metabolism in T-Cell Exhaustion

Key Points

Mitochondrial biogenesis and function are crucial for T cell activity and preventing exhaustion.
Interventions targeting mitochondrial metabolism can potentially reverse T cell exhaustion by enhancing ATP production.
Chronic antigenic stimulation leads to mitochondrial dysfunction, significantly influencing T cell differentiation and function.
Research covers strategies like alleviating ROS production and enhancing mitochondrial transfer to combat T cell exhaustion.

Abstract

T cells play a vital role in resisting pathogen invasion and maintaining immune homeostasis. However, T cells gradually become exhausted under chronic antigenic stimulation, and this exhaustion is closely related to mitochondrial dysfunction in T cells. Mitochondria play a crucial role in the metabolic reprogramming of T cells to achieve the desired immune response. Here, we compiled the latest research on how mitochondrial metabolism determines T cell function and differentiation, with the mechanisms mainly including mitochondrial biogenesis, fission, fusion, mitophagy, and mitochondrial transfer. In addition, the alterations in mitochondrial metabolism in T-cell exhaustion were also reviewed. Furthermore, we discussed intervention strategies targeting mitochondrial metabolism to reverse T cell exhaustion in detail, including inducing PGC-1α expression, alleviating reactive oxygen species (ROS) production or hypoxia, enhancing ATP production, and utilizing mitochondrial transfer. Targeting mitochondrial metabolism in exhausted T cells may achieve the goal of reversing and preventing T cell exhaustion.

Mitochondrial Metabolism in T-Cell Exhaustion

Key Points

Abstract

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