Mitochondrial calcium uniporter

Mitochondrial calcium uniporter
Identifiers
SymbolMCU
PfamPF04678
InterProIPR018782
TCDB1.A.77
OPM superfamily486
OPM protein6dnf
Membranome216
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Mitochondrial calcium uniporter
Identifiers
SymbolMCU
Alt. symbolsC10orf42, CCDC109A, FLJ46135
NCBI gene90550
HGNC23526
OMIM614197
PDBQ8NE86
RefSeqNM_138357
UniProtQ8NE86
Other data
LocusChr. 10 222
Search for
StructuresSwiss-model
DomainsInterPro

The mitochondrial calcium uniporter (MCU) is a transmembrane protein that allows the passage of calcium ions from a cell's cytosol into mitochondria. Its activity is regulated by MICU1 and MICU2, which together with the MCU make up the mitochondrial calcium uniporter complex.[1]

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.

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.[2]

Ruthenium red and Ru360 are typical reagents used to experimentally block the MCU to study its properties and role in mitochondrial signaling.[3][4]

  1. ^ "MCU - Calcium uniporter protein, mitochondrial precursor - Homo sapiens (Human)". UniProt.org. UniProt Consortium. Retrieved 2016-02-24.
  2. ^ Marchi S, Pinton P (March 2014). "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. PMC 3948548. PMID 24366263.
  3. ^ 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. S2CID 516473.
  4. ^ Matlib MA, Zhou Z, Knight S, Ahmed S, Choi KM, Krause-Bauer J, et al. (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): 10223–10231. doi:10.1074/jbc.273.17.10223. PMID 9553073.