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Our group showed for the first time that G0S2 promotes quiescence in hematopoietic stem cells by interacting with and retaining nucleolin around the nucleus. Herein, we report the role of G0S2 in the differentiation and function of CD8<jats:sup>+<\/jats:sup> T cells examined in mice with an embryonic deletion of the <jats:italic>G0s2<\/jats:italic> gene. G0S2 expression in na\u00efve CD8<jats:sup>+<\/jats:sup> T cells decreased immediately after T\u2010cell receptor activation downstream of the mitogen\u2010activated protein kinase, calcium\/calmodulin, phosphatidylinositol 3\u2032\u2010kinase and mammalian target of rapamycin pathways. Surprisingly, G0S2\u2010null na\u00efve CD8<jats:sup>+<\/jats:sup> T cells displayed increased basal and spare respiratory capacity that was not associated with increased mitochondrial biogenesis but with increased phosphorylation of AMP\u2010activated protein kinase \u03b1. Na\u00efve CD8<jats:sup>+<\/jats:sup> T cells showed increased proliferation in response to <jats:italic>in vitro<\/jats:italic> activation and <jats:italic>in vivo<\/jats:italic> lymphopenia; however, na\u00efve CD8<jats:sup>+<\/jats:sup> T cells expressing the OT\u20101 transgene exhibited normal differentiation of na\u00efve cells to effector and memory CD8<jats:sup>+<\/jats:sup> T cells upon infection with <jats:italic>Listeria monocytogenes<\/jats:italic> in a wild\u2010type or a <jats:italic>G0s2<\/jats:italic>\u2010null environment, with increased circulating levels of free fatty acids. Collectively, our results suggest that G0S2 inhibits energy production by oxidative phosphorylation to fine\u2010tune proliferation in homeostatic conditions.<\/jats:p>","DOI":"10.1038\/icb.2015.9","type":"journal-article","created":{"date-parts":[[2015,2,10]],"date-time":"2015-02-10T10:35:19Z","timestamp":1423564519000},"page":"605-615","source":"Crossref","is-referenced-by-count":17,"title":["G0S2 modulates homeostatic proliferation of na\u00efve CD8<sup>+<\/sup> T cells and inhibits oxidative phosphorylation in mitochondria"],"prefix":"10.1111","volume":"93","author":[{"given":"Ping\u2010Hsien","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's 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