Browsing by Author "Nicole A. Hofmann"

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    PRMT1-mediated methylation of MICU1 determines the UCP2/3 dependency of mitochondrial Ca2+ uptake in immortalized cells
    (2016-09-19) Corina T. Madreiter-Sokolowski; Christiane Klec; Warisara Parichatikanond; Sarah Stryeck; Benjamin Gottschalk; Sergio Pulido; Rene Rost; Emrah Eroglu; Nicole A. Hofmann; Alexander I. Bondarenko; Tobias Madl; Markus Waldeck-Weiermair; Roland Malli; Wolfgang F. Graier; Medizinische Universitat Graz; Karl-Franzens-Universitat Graz; Technical University of Munich; Helmholtz Center Munich German Research Center for Environmental Health; Mahidol University
    © 2016 The Author(s). Recent studies revealed that mitochondrial Ca2+ channels, which control energy flow, cell signalling and death, are macromolecular complexes that basically consist of the pore-forming mitochondrial Ca2+ uniporter (MCU) protein, the essential MCU regulator (EMRE), and the mitochondrial Ca2+ uptake 1 (MICU1). MICU1 is a regulatory subunit that shields mitochondria from Ca2+ overload. Before the identification of these core elements, the novel uncoupling proteins 2 and 3 (UCP2/3) have been shown to be fundamental for mitochondrial Ca2+ uptake. Here we clarify the molecular mechanism that determines the UCP2/3 dependency of mitochondrial Ca2+ uptake. Our data demonstrate that mitochondrial Ca2+ uptake is controlled by protein arginine methyl transferase 1 (PRMT1) that asymmetrically methylates MICU1, resulting in decreased Ca2+ sensitivity. UCP2/3 normalize Ca2+ sensitivity of methylated MICU1 and, thus, re-establish mitochondrial Ca2+ uptake activity. These data provide novel insights in the complex regulation of the mitochondrial Ca2+ uniporter by PRMT1 and UCP2/3.