TY - GEN A1 - Iwert, C. A1 - Stein, J. A1 - Appelt, C. A1 - Vogt, K. A1 - Rainer, R. J. A1 - Tummler, K. A1 - Mühle, K. A1 - Stanko, K. A1 - Schumann, J. A1 - Uebe, D. A1 - Jürchott, K. A1 - Lisec, Jan A1 - Janek, K. A1 - Gille, C. A1 - Textoris-Taube, K. A1 - Sai, S. A1 - Petersen, A. A1 - Kühl, A. A. A1 - Klipp, E. A1 - Meisel, C. A1 - Sawitzki, B. T1 - TCAIM controls effector T cell generation by preventing Mitochondria-Endoplasmic Reticulum Contact Site-initiated Cholesterol Biosynthesis N2 - T cells need to adapt their cellular metabolism for effector cell differentiation. This relies on alterations in mitochondrial physiology. Which signals and molecules regulate those alterations remains unclear. We recently reported, that the mitochondrial protein TCAIM inhibits activation-induced changes in mitochondrial morphology and function and thus, CD effector T cell formation. Using conditional TCAIM knock-in (KI) and knockout (KO) mice, w now show that it also applies to CD8+ T cells and more importantly, delineate the molecular processes in mitochondria by which TCAIM controls effector cell differentiation. TCAIM KI resulted in reduced activation-induced HIF1α protein expression. Metabolomics and transcriptional data in combination with mathematical flux modeling revealed an impaired induction of anabolic pathways, especially of the mevalonate pathway and cholesterol biosynthesis in TCAIM KI CD8+ T cells. Addition of cholesterol completely rescued HIF1α protein expression, activation and proliferation of TCAIM KI CD8+ T cells. At the molecular level, TCAIM delayed activation-induced mitochondria-ER contact (MERC) formation by binding to MERC promoting proteins such as RMD3 and VDAC2. In summary, we demonstrate that TCAIM suppresses effector cell differentiation by inhibiting MERC formation, which induce HIF1α-mediated increase in cellular metabolism and cholesterol biosynthesis. KW - Mass Spectroscopy KW - Metabolomics KW - Cancer PY - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:b43-533543 UR - https://www.biorxiv.org/content/10.1101/2021.04.20.440500v1 VL - April SP - 1 EP - 45 PB - Cold Spring Harbor Laboratory AN - OPUS4-53354 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Täube, D. A1 - Hahn, Oliver ED - Matthias Hamann, T1 - Kalte Malerei auf Glas KW - Kunst- und Kulturgut KW - Kunstgeschichte KW - Hinterglasmalerei PY - 2009 SN - 0933-257X SN - 0178-4218 IS - 2 SP - 54 EP - 61 PB - Museumsdienst Köln CY - Köln AN - OPUS4-19857 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bretz, S. A1 - Hagnau, C. A1 - Hahn, Oliver A1 - Ranz, H.-J. A1 - Täube, D. A1 - Wolff, Timo T1 - Was ist tatsächlich Schwarzlotmalerei? T2 - Jahrestagung in der Pinakothek der Moderne - Archäometrie und Denkmalpflege CY - München, Deutschland DA - 2009-03-25 KW - Archäometrie KW - Zerstörungsfreie Prüfung KW - Hinterglasmalerei PY - 2009 SN - 0947-6229 IS - 2 SP - 246 EP - 248 PB - Dt. Bergbau-Museum CY - Bochum AN - OPUS4-19336 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bretz, S. A1 - Hagnau, C. A1 - Hahn, Oliver A1 - Ranz, H.-J. A1 - Täube, D. T1 - Hinterglasmalerei im Mittelalter T2 - Jahrestagung in der Pinakothek der Moderne - Archäometrie und Denkmalpflege 2009 CY - München, Deutschland DA - 2009-03-25 KW - Archäometrie KW - Zerstörungsfreie Prüfung KW - Hinterglasmalerei PY - 2009 SN - 0947-6229 IS - 2 SP - 234 EP - 236 PB - Dt. Bergbau-Museum CY - Bochum AN - OPUS4-19335 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -