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Uniporter
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=== Mitochondrial {{chem2|Ca(2+)}} uniporter (MCU) === The '''mitochondrial calcium uniporter''' (MCU) is a protein complex located in the inner mitochondrial matrix that functions to take up calcium ions (Ca2+) into the [[Mitochondrial matrix|matrix]] from the [[cytoplasm]].<ref name="De Stefani D">{{cite journal |vauthors=De Stefani D, Patron M, Rizzuto R |title=Structure and function of the mitochondrial calcium uniporter complex |journal=Biochim Biophys Acta |volume=1853 |issue=9 |pages=2006β11 |date=September 2015 |pmid=25896525 |pmc=4522341 |doi=10.1016/j.bbamcr.2015.04.008 }}</ref> The transport of calcium ions is specifically used in cellular function for regulating energy production in the mitochondria, cytosolic [[calcium signaling]], and [[cell death]]. The uniporter becomes activated when cytoplasmic levels of calcium rise above 1 uM.<ref name="De Stefani D" /> The [[Mitochondrial calcium uniporter|MCU complex]] comprises 4 parts: the port-forming subunits, regulatory subunits [[MICU1 (gene)|MICU1]] and MICU2, and an auxiliary subunit, EMRE.<ref name="D'Angelo D">{{cite journal |vauthors=D'Angelo D, Rizzuto R |title=The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases |journal=Biomolecules |volume=13 |issue=9 |date=August 2023 |page=1304 |pmid=37759703 |pmc=10526485 |doi=10.3390/biom13091304 |doi-access=free }}</ref> These subunits work together to regulate the uptake of calcium in the mitochondria. Specifically, the EMRE subunit functions for the transport of calcium, and the MICU subunit functions in tightly regulating the activity of MCU to prevent the overload of calcium concentrations in the cytoplasm.<ref name="D'Angelo D" /> Calcium is fundamental for signaling pathways in cells, as well as for cell death pathways.<ref name="D'Angelo D" /> The function of the mitochondrial uniporter is critical for maintaining cellular [[homeostasis]]. The MICU1 and MICU2 subunits are a [[Protein dimer|heterodimer]] connected by a [[Disulfide|disulfide bridge]].<ref name="De Stefani D" /> When there are high levels of cytoplasmic calcium, the MICU1-MICU2 heterodimer undergoes a [[conformational change]].<ref name="De Stefani D" /> The heterodimer subunits have cooperative activation, which means {{chem2|Ca(2+)}} binding to one MICU subunit in the heterodimer induces a conformational change on the other MICU subunits. The uptake of calcium is balanced by the [[sodium-calcium exchanger]].<ref name="D'Angelo D" />
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