Corina T. Madreiter-SokolowskiChristiane KlecWarisara ParichatikanondSarah StryeckBenjamin GottschalkSergio PulidoRene RostEmrah ErogluNicole A. HofmannAlexander I. BondarenkoTobias MadlMarkus Waldeck-WeiermairRoland MalliWolfgang F. GraierMedizinische Universitat GrazKarl-Franzens-Universitat GrazTechnical University of MunichHelmholtz Center Munich German Research Center for Environmental HealthMahidol University2018-12-112019-03-142018-12-112019-03-142016-09-19Nature Communications. Vol.7, (2016)204117232-s2.0-84988474788https://repository.li.mahidol.ac.th/handle/20.500.14594/42973© 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryArticleSCOPUS10.1038/ncomms12897