2020
DOI: 10.3390/ijms21103642
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Structural Mechanisms of Store-Operated and Mitochondrial Calcium Regulation: Initiation Points for Drug Discovery

Abstract: Calcium (Ca2+) is a universal signaling ion that is essential for the life and death processes of all eukaryotes. In humans, numerous cell stimulation pathways lead to the mobilization of sarco/endoplasmic reticulum (S/ER) stored Ca2+, resulting in the propagation of Ca2+ signals through the activation of processes, such as store-operated Ca2+ entry (SOCE). SOCE provides a sustained Ca2+ entry into the cytosol; moreover, the uptake of SOCE-mediated Ca2+ by mitochondria can shape cytosolic Ca2+ signals, functio… Show more

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Cited by 7 publications
(6 citation statements)
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References 269 publications
(381 reference statements)
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“…In mammals, mitochondrial translation occurs in mitoribosomes, and these ribosomes produce proteins that play a part in oxidative phosphorylation [ 48 , 50 , 51 ]. As previously pointed out, there is a relation between SOCE and calcium regulation in mitochondria [ 52 , 53 , 54 , 55 ]. Our pathway enrichment results also support this hypothesis.…”
Section: Discussionmentioning
confidence: 99%
“…In mammals, mitochondrial translation occurs in mitoribosomes, and these ribosomes produce proteins that play a part in oxidative phosphorylation [ 48 , 50 , 51 ]. As previously pointed out, there is a relation between SOCE and calcium regulation in mitochondria [ 52 , 53 , 54 , 55 ]. Our pathway enrichment results also support this hypothesis.…”
Section: Discussionmentioning
confidence: 99%
“…and prolonged MCU pore opening may contribute to cell death. [81][82][83] Inhibiting MCU pore function, especially in the presence of high calcium levels, could potentially reduce ROS-mediated disease prevalence.…”
Section: Ru265 Complexmentioning
confidence: 99%
“…[31–33,37,50–53]). Heritable loss of MICU1 and MICU2 function mutations leads to disorders characterized by muscle weakness, fatigue, lethargy, developmental delay, and learning disabilities 21,54–57 . MICU1 knockout (KO) mouse studies highlight a complex gatekeeping function as fibroblast KO mitochondria at low and high cytosolic Ca 2+ show higher and lower rates of Ca 2+ uptake, respectively, 58 striated muscle KO mitochondria show increased basal but decreased Ca 2+ uptake rates after stimulus 59 and neuronal KO mitochondria show increased Ca 2+ uptake at subthreshold cytosolic Ca 2+ but reduced Ca 2+ uptake at high cytosolic Ca 2+ 60 …”
Section: Mitochondrial Calcium Uniporter Complex (Mtcu) Componentsmentioning
confidence: 99%
“…fatigue, lethargy, developmental delay, and learning disabilities. 21,[54][55][56][57] MICU1 knockout (KO) mouse studies highlight a complex gatekeeping function as fibroblast KO mitochondria at low and high cytosolic Ca 2+ show higher and lower rates of Ca 2+ uptake, respectively, 58 striated muscle KO mitochondria show increased basal but decreased Ca 2+ uptake rates after stimulus 59 and neuronal KO mitochondria show increased Ca 2+ uptake at subthreshold cytosolic Ca 2+ but reduced Ca 2+ uptake at high cytosolic Ca 2+ . 60 In low Ca 2+ , cryoEM revealed mtCU arrangements with MICU1 tightly occluding the pore entrance through electrostatic interactions between Lys/Arg residues of MICU1 and three of the DIME Asp261 residues of the MCU tetramer.…”
Section: Introductionmentioning
confidence: 99%
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