Mitochondrial calcium uniporter: Difference between revisions
New page: ==Mitochondrial Calcium Uniporter== <StructureSection load='6dnf' size='340' side='right' caption='Mitochondrial Calcium Uniporter (MCU): Each monomer is shown in a different color. Calciu... |
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== Overview == | == Overview == | ||
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 eukaryotes], but activity is regulated differently in each [https://en.wikipedia.org/wiki/Clade clade].<ref name="Baradaran">PMID:29995857</ref> MCU was definitively assigned in 2011 using a combination of [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance_spectroscopy NMR spectroscopy], [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryoelectron microscopy], and [https://en.wikipedia.org/wiki/X-ray_crystallography x-ray crystallography].<ref name="Woods">PMID:31869674</ref> Recent [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryoelectron microscopy] (cryo-EM) analysis provides a structural framework for understanding the mechanism for calcium selectivity by the MCU.<ref name="Giorgi" /> Like other ion channels, the MCU is highly selective and efficient, allowing 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"/> | 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 eukaryotes], but activity is regulated differently in each [https://en.wikipedia.org/wiki/Clade clade].<ref name="Baradaran">PMID:29995857</ref> MCU was definitively assigned in 2011 using a combination of [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance_spectroscopy NMR spectroscopy], [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryoelectron microscopy], and [https://en.wikipedia.org/wiki/X-ray_crystallography x-ray crystallography].<ref name="Woods">PMID:31869674</ref> Recent [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryoelectron microscopy] (cryo-EM) analysis provides a structural framework for understanding the mechanism for calcium selectivity by the MCU.<ref name="Giorgi" /> Like other ion channels, the MCU is highly selective and efficient, allowing 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 [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm], but when stimulated, mitochondrial calcium concentration increases 10 to 20-fold.<ref name="Giorgi">PMID:30143745</ref> [https://en.wikipedia.org/wiki/Mitochondria_associated_membranes Mitochondria-associated ER membranes] exist between the mitochondria and the [https://en.wikipedia.org/wiki/Endoplasmic_reticulum endoplasmic reticulum] facilitate efficient transport of calcium ions.<ref name="Wang">PMID:28882140</ref> The transfer of electrons through [https://en.wikipedia.org/wiki/Electron_transport_chain#Mitochondrial_redox_carriers respiratory complexes I-IV] produces the energy to pump [https://en.wikipedia.org/wiki/Hydrogen_ion hydrogen ions] into the intermembrane space and establish the proton [https://en.wikipedia.org/wiki/Electrochemical_gradient 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"/> Calcium uptake and efflux must be tightly regulated to controll essential [https://en.wikipedia.org/wiki/Citric_acid_cycle Krebs cycle] enzyme activity, including [http://proteopedia.org/wiki/index.php/Pyruvate_dehydrogenase pyruvate dehydrogenase], [https://en.wikipedia.org/wiki/Oxoglutarate_dehydrogenase_complex α-ketoglutarate dehydrogenase], and [http://proteopedia.org/wiki/index.php/Isocitrate_dehydrogenase isocitrate dehydrogenase], while avoiding calcium overload and [https://en.wikipedia.org/wiki/Apoptosis apoptosis].<ref name="Wang"/> | Under resting conditions, the calcium concentration in the mitochondria is about the same as in the [https://en.wikipedia.org/wiki/Cytoplasm cytoplasm], but when stimulated, mitochondrial calcium concentration increases 10 to 20-fold.<ref name="Giorgi">PMID:30143745</ref> [https://en.wikipedia.org/wiki/Mitochondria_associated_membranes Mitochondria-associated ER membranes] exist between the mitochondria and the [https://en.wikipedia.org/wiki/Endoplasmic_reticulum endoplasmic reticulum] facilitate efficient transport of calcium ions.<ref name="Wang">PMID:28882140</ref> The transfer of electrons through [https://en.wikipedia.org/wiki/Electron_transport_chain#Mitochondrial_redox_carriers respiratory complexes I-IV] produces the energy to pump [https://en.wikipedia.org/wiki/Hydrogen_ion hydrogen ions] into the intermembrane space and establish the proton [https://en.wikipedia.org/wiki/Electrochemical_gradient 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"/> Calcium uptake and efflux must be tightly regulated to controll essential [https://en.wikipedia.org/wiki/Citric_acid_cycle Krebs cycle] enzyme activity, including [http://proteopedia.org/wiki/index.php/Pyruvate_dehydrogenase pyruvate dehydrogenase], [https://en.wikipedia.org/wiki/Oxoglutarate_dehydrogenase_complex α-ketoglutarate dehydrogenase], and [http://proteopedia.org/wiki/index.php/Isocitrate_dehydrogenase isocitrate dehydrogenase], while avoiding calcium overload and [https://en.wikipedia.org/wiki/Apoptosis apoptosis].<ref name="Wang"/> | ||
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