PRMT1-mediated methylation of MICU1 determines the UCP2/3 dependency of mitochondrial Ca2+ uptake in immortalized cells
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...
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Published in | Nature communications Vol. 7; no. 1; pp. 12897 - 13 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
19.09.2016
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
MICU1 is a regulatory subunit of mitochondrial Ca
2+
channels that shields mitochondria from Ca
2+
overload. Here the authors show that MICU1 methylation by PRMT1 reduces Ca
2+
sensitivity, which is normalized by UCP2/3, re-establishing mitochondrial Ca
2+
uptake activity. |
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Bibliography: | Present address: Department of Pharmacology, Mahidol University, Bangkok 10400, Thailand |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms12897 |