Sandbox Reserved 1626: Difference between revisions

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== Overview ==
== Overview ==
[https://en.wikipedia.org/wiki/Insulin insulin]


[[Image:Ruthenium_Red.jpg|300 px|right|thumb|'''Fig. 2''' Structure of Ruthenium Red]]
[[Image:Ruthenium_Red.jpg|300 px|right|thumb|'''Fig. 2''' Structure of Ruthenium Red]]


The mitochondrial calcium uniporter (MCU) complex is the main source of entry for [https://en.wikipedia.org/wiki/Calcium calcium] ions into the mitochondrial matrix from the intermembrane space.  MCU channels exist in most eukaryotic life, but activity is regulated differently in each clade.<ref name="Baradaran">PMID:29995857</ref> The precise identity of the MCU wasn't discovered until 2011 and was discovered using a combination of NMR spectroscopy, cryo-electron microscopy, and x-ray crystallography.<ref name="Woods">PMID:31869674</ref> Identification of the structure was difficult because it has no apparent sequence similarity to other ion channels.<ref name="Baradaran"/> However, like other ion channels, it is incredibly selective and efficient.  The MCU has the ability to only allow calcium ions into the mitochondrial matrix at a rate of 5,000,000 ions per second even though potassium ions are over 100,000 times more abundant in the intermembrane space.<ref name="Baradaran"/>  
The mitochondrial calcium uniporter (MCU) complex is the main source of entry for [https://en.wikipedia.org/wiki/Calcium calcium] ions into the [https://en.wikipedia.org/wiki/Mitochondrial_matrix mitochondrial matrix] from the [https://en.wikipedia.org/wiki/Mitochondrion#Intermembrane_space intermembrane space].  MCU channels exist in most [https://en.wikipedia.org/wiki/Eukaryote eukaryotic] life, but activity is regulated differently in each [https://en.wikipedia.org/wiki/Clade clade].<ref name="Baradaran">PMID:29995857</ref> The precise identity of the MCU wasn't discovered until 2011 and was discovered using a combination of [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance_spectroscopy NMR spectroscopy], [https://en.wikipedia.org/wiki/Transmission_electron_cryomicroscopy cryo-electron microscopy], and [https://en.wikipedia.org/wiki/X-ray_crystallography x-ray crystallography].<ref name="Woods">PMID:31869674</ref> Identification of the structure was difficult because it has no apparent sequence similarity to other ion channels.<ref name="Baradaran"/> However, like other ion channels, it is incredibly selective and efficient.  The MCU has the ability to only allow calcium ions into the mitochondrial matrix at a rate of 5,000,000 ions per second even though [https://en.wikipedia.org/wiki/Potassium potassium] ions are over 100,000 times more abundant in the intermembrane space.<ref name="Baradaran"/>  


Under resting conditions, the calcium concentration in the mitochondria is about the same as in the cytoplasm, but when stimulated, it can increase calcium concentration 10-20-fold.<ref name="Giorgi">PMID:30143745</ref>  Mitochondria-associated ER membranes (MAMs) exist between mitochondria and the endoplasmic reticulum, the two largest cellular stores of calcium, to allow for efficient transport of calcium ions.<ref name="Wang">PMID:28882140</ref>  The transfer of electrons through respiratory complexes I-IV produces the energy to pump hydrogen ions into the intermembrane space (IMS) and create the proton electrochemical gradient potential.<ref name="Giorgi"/> This negative electrochemical potential is the driving force that moves positively charged calcium ions into the mitochondrial matrix.<ref name="Giorgi"/>
Under resting conditions, the calcium concentration in the mitochondria is about the same as in the cytoplasm, but when stimulated, it can increase calcium concentration 10-20-fold.<ref name="Giorgi">PMID:30143745</ref>  Mitochondria-associated ER membranes (MAMs) exist between mitochondria and the endoplasmic reticulum, the two largest cellular stores of calcium, to allow for efficient transport of calcium ions.<ref name="Wang">PMID:28882140</ref>  The transfer of electrons through respiratory complexes I-IV produces the energy to pump hydrogen ions into the intermembrane space (IMS) and create the proton electrochemical gradient potential.<ref name="Giorgi"/> This negative electrochemical potential is the driving force that moves positively charged calcium ions into the mitochondrial matrix.<ref name="Giorgi"/>