PRMT1-mediated methylation of MICU1 determines the UCP2/3 dependency of mitochondrial Ca(2+) uptake in immortalized cells.
PRMT1-mediated methylation of MICU1 determines the UCP2/3 dependency of mitochondrial Ca(2+) uptake in immortalized cells.
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DOI：
10.1038/ncomms12897
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发表时间：
2016-09-19
影响因子：
16.6
通讯作者：
Graier, Wolfgang F.
中科院分区：
文献类型：
--
作者：
Madreiter-Sokolowski, Corina T.;Klec, Christiane;Parichatikanond, Warisara;Stryeck, Sarah;Gottschalk, Benjamin;Pulido, Sergio;Rost, Rene;Eroglu, Emrah;Hofmann, Nicole A.;Bondarenko, Alexander I.;Madl, Tobias;Waldeck-Weiermair, Markus;Malli, Roland;Graier, Wolfgang F.
最近的研究表明，线粒体Ca 2+通道，控制能量流动，细胞信号传导和死亡，是大分子复合物，基本上由成孔线粒体Ca 2+单向转运体（MCU）蛋白，必需MCU调节器（EMRE）和线粒体Ca 2+摄取1（MICU 1）组成。MICU 1是一个保护线粒体免受Ca 2+超载的调节亚基。在确定这些核心元件之前，新的解偶联蛋白2和3（UCP 2/3）已被证明是线粒体Ca 2+摄取的基础。在这里，我们澄清的分子机制，决定了UCP 2/3的依赖性线粒体Ca 2+摄取。我们的数据表明，线粒体Ca 2+摄取是由蛋白质精氨酸甲基转移酶1（PRMT 1），不对称甲基化MICU 1，导致Ca 2+敏感性降低。UCP 2/3使甲基化MICU 1的Ca 2+敏感性正常化，从而重新建立线粒体Ca 2+摄取活性。这些数据为PRMT 1和UCP 2/3对线粒体Ca 2+单向转运体的复杂调控提供了新的见解。 MICU 1是线粒体Ca 2+通道的调节亚基，其保护线粒体免于Ca 2+过载。在这里，作者表明PRMT 1的MICU 1甲基化降低了Ca 2+敏感性，这通过UCP 2/3标准化，重新建立了线粒体Ca 2+摄取活性。
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. MICU1 is a regulatory subunit of mitochondrial Ca2+ channels that shields mitochondria from Ca2+ overload. Here the authors show that MICU1 methylation by PRMT1 reduces Ca2+ sensitivity, which is normalized by UCP2/3, re-establishing mitochondrial Ca2+ uptake activity.
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DOI：
10.1074/jbc.m110.216044
发表时间：
2011-09-16
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
De Marchi U;Castelbou C;Demaurex N
通讯作者：
Demaurex N
影响因子：
3.3
作者：
Hoffman NE;Chandramoorthy HC;Shanmughapriya S;Zhang XQ;Vallem S;Doonan PJ;Malliankaraman K;Guo S;Rajan S;Elrod JW;Koch WJ;Cheung JY;Madesh M
通讯作者：
Madesh M
内膜的四十千克蛋白是线粒体钙Uniporter。
影响因子：
64.8
作者：
De Stefani, Diego;Raffaello, Anna;Teardo, Enrico;Szabo, Ildiko;Rizzuto, Rosario
通讯作者：
Rizzuto, Rosario
DOI：
10.1016/j.bbamcr.2015.04.008
发表时间：
2015-09
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
De Stefani D;Patron M;Rizzuto R
通讯作者：
Rizzuto R
影响因子：
8.8
作者：
Hoffman NE;Chandramoorthy HC;Shamugapriya S;Zhang X;Rajan S;Mallilankaraman K;Gandhirajan RK;Vagnozzi RJ;Ferrer LM;Sreekrishnanilayam K;Natarajaseenivasan K;Vallem S;Force T;Choi ET;Cheung JY;Madesh M
通讯作者：
Madesh M