PRMT1-mediated methylation of MICU1 determines the UCP2/3 dependency of mitochondrial Ca2+ uptake in immortalized cells
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 and
Wolfgang F. Graier ()
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Corina T. Madreiter-Sokolowski: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Christiane Klec: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Warisara Parichatikanond: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Sarah Stryeck: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Benjamin Gottschalk: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Sergio Pulido: Institute of Chemistry, University of Graz
Rene Rost: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Emrah Eroglu: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Nicole A. Hofmann: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Alexander I. Bondarenko: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Tobias Madl: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Markus Waldeck-Weiermair: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Roland Malli: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Wolfgang F. Graier: Center for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz
Nature Communications, 2016, vol. 7, issue 1, 1-13
Abstract:
Abstract 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.
Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12897
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DOI: 10.1038/ncomms12897
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