Abstract
Effector T cells rely on tightly coordinated metabolic and epigenetic programs to sustain immune function. Emerging evidence highlights a central role for mitochondria in integrating these programs through nutrient utilization and regulation of metabolite flux. The electron transport chain (ETC), localized to the inner mitochondrial membrane, directs cellular metabolism toward oxidative phosphorylation. The efficiency of ETC activity is governed by the highly folded architecture of the inner mitochondrial membrane into cristae. Although mitochondrial metabolism is well recognized as a key determinant of cellular metabolic states, the regulatory roles of cristae-organizing structural proteins, particularly in T cells, remain poorly defined. Our recent study identifies the inner mitochondrial membrane protein TMEM11 as a critical structural determinant of cristae organization and demonstrates how cristae integrity governs effector T cell function by controlling oxidative phosphorylation and metabolite flux. TMEM11 deficiency disrupts cristae architecture in T cells without affecting mitochondrial biogenesis or cell viability. Mechanistically, loss of TMEM11 impairs ETC function, leading to elevated mitochondrial reactive oxygen species (mtROS), which diverts acetyl-CoA away from histone acetylation toward fatty acid synthesis, thereby suppressing cytokine production. Collectively, these findings reveal a structural-metabolic-epigenetic axis that is essential for effector T cell immunity and suggest potential relevance for T cell-mediated cancer therapy.
Keywords
Effector T cells, Mitochondria, Cristae, Reactive oxygen species