PT - JOURNAL ARTICLE AU - Taku Kuwabara AU - Fumio Ishikawa AU - Masataka Ikeda AU - Tomomi Ide AU - Terumi Kohwi-Shigematsu AU - Yuriko Tanaka AU - Motonari Kondo TI - SATB1-dependent mitochondrial ROS production controls TCR signaling in CD4 T cells AID - 10.26508/lsa.202101093 DP - 2021 Nov 01 TA - Life Science Alliance PG - e202101093 VI - 4 IP - 11 4099 - https://www.life-science-alliance.org/content/4/11/e202101093.short 4100 - https://www.life-science-alliance.org/content/4/11/e202101093.full SO - Life Sci. Alliance2021 Nov 01; 4 AB - Special AT-rich sequence binding protein-1 (SATB1) is localized to the nucleus and remodels chromatin structure in T cells. SATB1-deficient CD4 T cells cannot respond to TCR stimulation; however, the cause of this unresponsiveness is to be clarified. Here, we demonstrate that SATB1 is indispensable to proper mitochondrial functioning and necessary for the activation of signal cascades via the TCR in CD4 T cells. Naïve SATB1-deficient CD4 T cells contain fewer mitochondria than WT T cells, as the former do not express mitochondrial transcription factor A (TFAM). Impaired mitochondrial function in SATB1-deficient T cells subverts mitochondrial ROS production and SHP-1 inactivation by constitutive oxidization. Ectopic TFAM expression increases mitochondrial mass and mitochondrial ROS production and rescues defects in the antigen-specific response in the SATB1-deficient T cells. Thus, SATB1 is vital for maintaining mitochondrial mass and function by regulating TFAM expression, which is necessary for TCR signaling.