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Madreiter-Sokolowski, CT; Klec, C; Parichatikanond, W; Stryeck, S; Gottschalk, B; Pulido, S; Rost, R; Eroglu, E; Hofmann, NA; Bondarenko, AI; Madl, T; Waldeck-Weiermair, M; Malli, R; Graier, WF.
PRMT1-mediated methylation of MICU1 determines the UCP2/3 dependency of mitochondrial Ca(2+) uptake in immortalized cells.
Nat Commun. 2016; 7(4):12897-12897
Doi: 10.1038/ncomms12897
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- Leading authors Med Uni Graz
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Graier Wolfgang
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Madreiter-Sokolowski Corina
- Co-authors Med Uni Graz
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Bondarenko Oleksandr
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EROGLU Emrah
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Gottschalk Benjamin
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Hofmann Nicole
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Klec Christiane
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Madl Tobias
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Malli Roland
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Parichatikanond Warisara
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Rost René
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Stryeck Sarah
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Waldeck-Weiermair Markus
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- Abstract:
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Recent studies revealed that mitochondrial Ca(2+) channels, which control energy flow, cell signalling and death, are macromolecular complexes that basically consist of the pore-forming mitochondrial Ca(2+) uniporter (MCU) protein, the essential MCU regulator (EMRE), and the mitochondrial Ca(2+) uptake 1 (MICU1). MICU1 is a regulatory subunit that shields mitochondria from Ca(2+) 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 Ca(2+) uptake. Here we clarify the molecular mechanism that determines the UCP2/3 dependency of mitochondrial Ca(2+) uptake. Our data demonstrate that mitochondrial Ca(2+) uptake is controlled by protein arginine methyl transferase 1 (PRMT1) that asymmetrically methylates MICU1, resulting in decreased Ca(2+) sensitivity. UCP2/3 normalize Ca(2+) sensitivity of methylated MICU1 and, thus, re-establish mitochondrial Ca(2+) uptake activity. These data provide novel insights in the complex regulation of the mitochondrial Ca(2+) uniporter by PRMT1 and UCP2/3.
- Find related publications in this database (using NLM MeSH Indexing)
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Calcium - metabolism
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Calcium Channels - metabolism
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Calcium-Binding Proteins - metabolism
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Cation Transport Proteins - metabolism
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HeLa Cells -
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Humans -
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Methylation -
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Mitochondrial Membrane Transport Proteins - metabolism
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Protein Processing, Post-Translational -
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Protein-Arginine N-Methyltransferases - metabolism
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Repressor Proteins - metabolism
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Uncoupling Protein 2 - metabolism
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Uncoupling Protein 3 - metabolism