Nature Immunology, Published online: 16 July 2025; doi:10.1038/s41590-025-02202-x

Mitochondrial electron transport chain activity provides ATP, generates superoxide, regulates apoptosis and provides the biosynthetic building blocks for growing cells. Here Steinert et al. genetically dissect these functions and find that, in the absence of mitochondrial complex III function, acute stimulation results in CD8+ T cell exhaustion and that mitochondrial complex III reactive oxygen species are required for establishment of naive and memory populations.



Summary

Steinert et al. in Nature Immunology (2025) explore the role of mitochondrial electron transport chain (ETC) complex III in CD8+ T cell function. Using genetic manipulation, they discovered that a lack of complex III activity leads to CD8+ T cell exhaustion upon acute stimulation. Furthermore, the study reveals that reactive oxygen species (ROS) produced by mitochondrial complex III are crucial for establishing naive and memory CD8+ T cell populations. These findings highlight the critical and nuanced role of the mitochondrial ETC in regulating T cell immunity and suggest potential therapeutic targets for modulating T cell responses.

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