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10.1016/j.jbc.2021.101174 http://scihub22266oqcxt.onion/10.1016/j.jbc.2021.101174 34499925!8496184!34499925     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Biol+Chem 2021 ; 297 (4): 101174 Nephropedia Template TP {{tp|p=34499925|t=2021. The Mitochondrial Ca(2+) uniporter is a central regulator of interorganellar Ca(2+) transfer and NFAT activation |pdf=|usr=}}{{34499925}} gab.com Text The Mitochondrial Ca(2+) uniporter is a central regulator of interorganellar Ca(2+) transfer and NFAT activation JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=34499925 #FOAvip Mitochondrial Ca(2+) uptake tailors the strength of stimulation of plasma membrane phospholipase C-coupled receptors to that of cellular bioenergetics. However, how Ca(2+) uptake by the mitochondrial Ca(2+) uniporter (MCU) shapes receptor-evoked interorganellar Ca(2+) signaling is unknown. Here, we used CRISPR/Cas9 gene knockout, subcellular Ca(2+) imaging, and mathematical modeling to show that MCU is a universal regulator of intracellular Ca(2+) signaling across mammalian cell types. MCU activity sustains cytosolic Ca(2+) signaling by preventing Ca(2+)-dependent inactivation of store-operated Ca(2+) release-activated Ca(2+) channels and by inhibiting Ca(2+) extrusion. Paradoxically, MCU knockout (MCU-KO) enhanced cytosolic Ca(2+) responses to store depletion. Physiological agonist stimulation in MCU-KO cells led to enhanced frequency of cytosolic Ca(2+) oscillations, endoplasmic reticulum Ca(2+) refilling, nuclear translocation of nuclear factor for activated T cells transcription factors, and cell proliferation, without altering inositol-1,4,5-trisphosphate receptor activity. Our data show that MCU has dual counterbalancing functions at the cytosol-mitochondria interface, whereby the cell-specific MCU-dependent cytosolic Ca(2+) clearance and buffering capacity of mitochondria reciprocally regulate interorganellar Ca(2+) transfer and nuclear factor for activated T cells nuclear translocation during receptor-evoked signaling. These findings highlight the critical dual function of the MCU not only in the acute Ca(2+) buffering by mitochondria but also in shaping endoplasmic reticulum and cytosolic Ca(2+) signals that regulate cellular transcription and function. Twit Text FOAVip The Mitochondrial Ca(2+) uniporter is a central regulator of interorganellar Ca(2+) transfer and NFAT activation ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=34499925 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34499925 #FOAvip English Wikipedia <ref>{{Cite pmid|34499925}}</ref> The Mitochondrial Ca(2+) uniporter is a central regulator of interorganellar Ca(2+) transfer and NFAT activation #MMPMID34499925 Yoast RE; Emrich SM; Zhang X; Xin P; Arige V; Pathak T; Benson JC; Johnson MT; Abdelnaby AE; Lakomski N; Hempel N; Han JM; Dupont G; Yule DI; Sneyd J; Trebak M J Biol Chem 2021[Oct]; 297 (4): 101174 PMID34499925show ga Mitochondrial Ca(2+) uptake tailors the strength of stimulation of plasma membrane phospholipase C-coupled receptors to that of cellular bioenergetics. However, how Ca(2+) uptake by the mitochondrial Ca(2+) uniporter (MCU) shapes receptor-evoked interorganellar Ca(2+) signaling is unknown. Here, we used CRISPR/Cas9 gene knockout, subcellular Ca(2+) imaging, and mathematical modeling to show that MCU is a universal regulator of intracellular Ca(2+) signaling across mammalian cell types. MCU activity sustains cytosolic Ca(2+) signaling by preventing Ca(2+)-dependent inactivation of store-operated Ca(2+) release-activated Ca(2+) channels and by inhibiting Ca(2+) extrusion. Paradoxically, MCU knockout (MCU-KO) enhanced cytosolic Ca(2+) responses to store depletion. Physiological agonist stimulation in MCU-KO cells led to enhanced frequency of cytosolic Ca(2+) oscillations, endoplasmic reticulum Ca(2+) refilling, nuclear translocation of nuclear factor for activated T cells transcription factors, and cell proliferation, without altering inositol-1,4,5-trisphosphate receptor activity. Our data show that MCU has dual counterbalancing functions at the cytosol-mitochondria interface, whereby the cell-specific MCU-dependent cytosolic Ca(2+) clearance and buffering capacity of mitochondria reciprocally regulate interorganellar Ca(2+) transfer and nuclear factor for activated T cells nuclear translocation during receptor-evoked signaling. These findings highlight the critical dual function of the MCU not only in the acute Ca(2+) buffering by mitochondria but also in shaping endoplasmic reticulum and cytosolic Ca(2+) signals that regulate cellular transcription and function. |*Calcium Signaling[MESH] |CRISPR-Cas Systems[MESH] |Calcium Channels/genetics/*metabolism[MESH] |Calcium/*metabolism[MESH] |Cytosol/*metabolism[MESH] |Endoplasmic Reticulum[MESH] |Gene Knockout Techniques[MESH] |HCT116 Cells[MESH] |HEK293 Cells[MESH] |Humans[MESH] |Jurkat Cells[MESH] |Lymphocyte Activation[MESH] |Mitochondria/*metabolism[MESH] |NFATC Transcription Factors/genetics/*metabolism[MESH]The Mitochondrial Ca(2+) uniporter is a central regulator of interorga(epmc).pdf DeepDyve Pubget Overpricing