Mitochondrial calcium uniporter

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), 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. 1 2 "Mitochondrial Calcium Uniporter". Tocris.com. Tocris Bioscience. 2016. Retrieved 2016-02-24.
  2. ↑ "MCU - Calcium uniporter protein, mitochondrial precursor - Homo sapiens (Human)". UniProt.org. UniProt Consortium. Retrieved 2016-02-24.
  3. ↑ Marchi, Saverio; Pinton, Paolo (2014-03-01). "The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications". The Journal of Physiology 592 (5): 829–839. doi:10.1113/jphysiol.2013.268235. ISSN 1469-7793. PMC 3948548. PMID 24366263.
  4. ↑ Broekemeier, K. M.; Krebsbach, R. J.; Pfeiffer, D. R. (1994-10-12). "Inhibition of the mitochondrial Ca2+ uniporter by pure and impure ruthenium red". Molecular and Cellular Biochemistry 139 (1): 33–40. ISSN 0300-8177. PMID 7531818.
  5. ↑ Matlib, M. A.; Zhou, Z.; Knight, S.; Ahmed, S.; Choi, K. M.; Krause-Bauer, J.; Phillips, R.; Altschuld, R.; Katsube, Y. (1998-04-24). "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): 10223–10231. ISSN 0021-9258. PMID 9553073.
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