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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.<\/jats:p>","DOI":"10.1038\/s42003-026-10522-3","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:47:09Z","timestamp":1784540829000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prohibitin 2 is a key regulator of T cell proliferation, differentiation, and effector functions in vivo"],"prefix":"10.1038","volume":"9","author":[{"given":"Johannes F.","family":"Vogt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8895-3495","authenticated-orcid":false,"given":"Carsten","family":"Merkwirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Adams-Quack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Zurkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanouill","family":"Stylianakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Uhlfelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Michna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2106-9179","authenticated-orcid":false,"given":"Assel","family":"Nurbekova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-6384","authenticated-orcid":false,"given":"Ute","family":"Distler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Rojas-Charry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Yurugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Rei\u00dfig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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