Mitochondrial calcium uniporter: Difference between revisions
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The MCU is one of the primary sources of mitochondria uptake of calcium, and flow is dependent on [[membrane potential]] of the [[inner mitochondrial membrane]] and the concentration of calcium in the cytosol relative to the concentration in the mitochondria. Balancing calcium concentration is necessary to increase the cell's energy supply and regulate cell death. Calcium is balanced through the MCU in conjunction with the [[sodium-calcium exchanger]].<ref name=":0" /> | The MCU is one of the primary sources of mitochondria uptake of calcium, and flow is dependent on [[membrane potential]] of the [[inner mitochondrial membrane]] and the concentration of calcium in the cytosol relative to the concentration in the mitochondria. Balancing calcium concentration is necessary to increase the cell's energy supply and regulate cell death. Calcium is balanced through the MCU in conjunction with the [[sodium-calcium exchanger]].<ref name=":0" /> | ||
The MCU has a very low [[Affinity (pharmacology)|affinity]] for calcium, so the cytosolic calcium concentration needs to be approximately 5-10 uM for significant transport of calcium into the mitochondria. Mitochondria are closely associated with the [[endoplasmic reticulum]] (ER), at contact sites, which contains stores of cellular calcium ions for [[calcium signaling]]. The presence of [[Inositol trisphosphate|1,4,5-triphosphate]] (IP<sub>3</sub>) triggers the release of calcium from these intracellular stores, which creates microdomains of high calcium concentration between the ER and the mitochondria, creating the conditions for the MCU to take up calcium.<ref>{{cite journal | vauthors = Marchi S, Pinton P | title = The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications | journal = The Journal of Physiology | volume = 592 | issue = 5 | pages = 829–39 | date = March 2014 | pmid = 24366263 | pmc = 3948548 | doi = 10.1113/jphysiol.2013.268235 | The MCU has a very low [[Affinity (pharmacology)|affinity]] for calcium, so the cytosolic calcium concentration needs to be approximately 5-10 uM for significant transport of calcium into the mitochondria. Mitochondria are closely associated with the [[endoplasmic reticulum]] (ER), at contact sites, which contains stores of cellular calcium ions for [[calcium signaling]]. The presence of [[Inositol trisphosphate|1,4,5-triphosphate]] (IP<sub>3</sub>) triggers the release of calcium from these intracellular stores, which creates microdomains of high calcium concentration between the ER and the mitochondria, creating the conditions for the MCU to take up calcium.<ref>{{cite journal | vauthors = Marchi S, Pinton P | title = The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications | journal = The Journal of Physiology | volume = 592 | issue = 5 | pages = 829–39 | date = March 2014 | pmid = 24366263 | pmc = 3948548 | doi = 10.1113/jphysiol.2013.268235 }}</ref> | ||
[[Ruthenium red]] and [[Ru360]] are typical reagents used to experimentally block the MCU to study its properties and role in mitochondrial signaling.<ref>{{cite journal | vauthors = Broekemeier KM, Krebsbach RJ, Pfeiffer DR | title = Inhibition of the mitochondrial Ca2+ uniporter by pure and impure ruthenium red | journal = Molecular and Cellular Biochemistry | volume = 139 | issue = 1 | pages = 33–40 | date = October 1994 | pmid = 7531818 | doi = 10.1007/bf00944201 }}</ref><ref>{{cite journal | vauthors = Matlib MA, Zhou Z, Knight S, Ahmed S, Choi KM, Krause-Bauer J, Phillips R, Altschuld R, Katsube Y, Sperelakis N, Bers DM | title = Oxygen-bridged dinuclear ruthenium amine complex specifically inhibits Ca2+ uptake into mitochondria in vitro and in situ in single cardiac myocytes | journal = The Journal of Biological Chemistry | volume = 273 | issue = 17 | pages = 10223–31 | date = April 1998 | pmid = 9553073 | doi = 10.1074/jbc.273.17.10223 }}</ref> | [[Ruthenium red]] and [[Ru360]] are typical reagents used to experimentally block the MCU to study its properties and role in mitochondrial signaling.<ref>{{cite journal | vauthors = Broekemeier KM, Krebsbach RJ, Pfeiffer DR | title = Inhibition of the mitochondrial Ca2+ uniporter by pure and impure ruthenium red | journal = Molecular and Cellular Biochemistry | volume = 139 | issue = 1 | pages = 33–40 | date = October 1994 | pmid = 7531818 | doi = 10.1007/bf00944201 }}</ref><ref>{{cite journal | vauthors = Matlib MA, Zhou Z, Knight S, Ahmed S, Choi KM, Krause-Bauer J, Phillips R, Altschuld R, Katsube Y, Sperelakis N, Bers DM | title = Oxygen-bridged dinuclear ruthenium amine complex specifically inhibits Ca2+ uptake into mitochondria in vitro and in situ in single cardiac myocytes | journal = The Journal of Biological Chemistry | volume = 273 | issue = 17 | pages = 10223–31 | date = April 1998 | pmid = 9553073 | doi = 10.1074/jbc.273.17.10223 }}</ref> | ||
Latest revision as of 15:47, 8 January 2019
| Mitochondrial calcium uniporter | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | MCU | ||||||||
| Pfam | PF04678 | ||||||||
| InterPro | IPR018782 | ||||||||
| TCDB | 1.A.77 | ||||||||
| OPM superfamily | 486 | ||||||||
| OPM protein | 6dnf | ||||||||
| Membranome | 216 | ||||||||
| |||||||||
| Mitochondrial calcium uniporter | |
|---|---|
| Identifiers | |
| Symbol | MCU |
| Alt. symbols | C10orf42, CCDC109A, FLJ46135 |
| Entrez | 90550 |
| HUGO | 23526 |
| OMIM | 614197 |
| PDB | Q8NE86 |
| RefSeq | NM_138357 |
| UniProt | Q8NE86 |
| Other data | |
| Locus | Chr. 10 222 |
The mitochondrial calcium uniporter (MCU) is a transmembrane protein that allows the passage of calcium ions from a cell's cytosol into mitochondria.[1] Its activity is regulated by MICU1 and MICU2, which together with the MCU make up the mitochondrial calcium uniporter complex.[2]
The MCU is one of the primary sources of mitochondria uptake of calcium, and flow is dependent on membrane potential of the inner mitochondrial membrane and the concentration of calcium in the cytosol relative to the concentration in the mitochondria. Balancing calcium concentration is necessary to increase the cell's energy supply and regulate cell death. Calcium is balanced through the MCU in conjunction with the sodium-calcium exchanger.[1]
The MCU has a very low affinity for calcium, so the cytosolic calcium concentration needs to be approximately 5-10 uM for significant transport of calcium into the mitochondria. Mitochondria are closely associated with the endoplasmic reticulum (ER), at contact sites, which contains stores of cellular calcium ions for calcium signaling. The presence of 1,4,5-triphosphate (IP3) triggers the release of calcium from these intracellular stores, which creates microdomains of high calcium concentration between the ER and the mitochondria, creating the conditions for the MCU to take up calcium.[3]
Ruthenium red and Ru360 are typical reagents used to experimentally block the MCU to study its properties and role in mitochondrial signaling.[4][5]
References
- ↑ 1.0 1.1 "Mitochondrial Calcium Uniporter". Tocris.com. Tocris Bioscience. 2016. Retrieved 2016-02-24.
- ↑ "MCU - Calcium uniporter protein, mitochondrial precursor - Homo sapiens (Human)". UniProt.org. UniProt Consortium. Retrieved 2016-02-24.
- ↑ Marchi S, Pinton P (March 2014). "The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications". The Journal of Physiology. 592 (5): 829–39. doi:10.1113/jphysiol.2013.268235. PMC 3948548. PMID 24366263.
- ↑ Broekemeier KM, Krebsbach RJ, Pfeiffer DR (October 1994). "Inhibition of the mitochondrial Ca2+ uniporter by pure and impure ruthenium red". Molecular and Cellular Biochemistry. 139 (1): 33–40. doi:10.1007/bf00944201. PMID 7531818.
- ↑ Matlib MA, Zhou Z, Knight S, Ahmed S, Choi KM, Krause-Bauer J, Phillips R, Altschuld R, Katsube Y, Sperelakis N, Bers DM (April 1998). "Oxygen-bridged dinuclear ruthenium amine complex specifically inhibits Ca2+ uptake into mitochondria in vitro and in situ in single cardiac myocytes". The Journal of Biological Chemistry. 273 (17): 10223–31. doi:10.1074/jbc.273.17.10223. PMID 9553073.