Prohibitin 2 is a key regulator of T cell proliferation, differentiation, and effector functions in vivo.

Prohibitin 2 (PHB2) is a highly conserved protein with essential roles in cell homeostasis and survival across different cell types. Previous studies have shown that the deletion of PHB2 results in an arrest in proliferation due to impaired mitochondrial function regulated by the dynamin-like GTPase OPA1. The function of PHB2 in immune cells remains unclear; however, some studies suggest that PHB2 plays a role in the cell membranes of B and T cells. In order to elucidate the role of PHB2 in immune cells, we generated PHB2-deficient T cells. Our findings reveal a pivotal role for PHB2 in the proliferation and differentiation of T cells. PHB2 deficiency inhibits T cell proliferation by inducing a cell cycle arrest at the G1 to S phase, thereby preventing the differentiation into effector T cells. Furthermore, in contrast to previous reports, T cells lacking PHB2 are more resistant to apoptosis. Metabolic analysis reveals that PHB2-deficient T cells fail to boost their energy production through glycolysis and oxidative phosphorylation upon activation, hindering their ability to sustain biosynthetic processes and to proliferate in response to activation.