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were discovered scientists made some intriguing discoveries in regards to the two proteins. Both MICU1 and MCU share similar RNA sequences, same pattern of expression, and they both interact with one another in the intermitochondrial membrane. It was first found through the use of siRNA screening of the membrane. The functions of MICU1 are still being studied; however, there are some important functions MICU1 plays in the intermitochondrial membrane. MICU1 helps to stabilize the entire mitochondrial calcium uniporter complex, it also limits the amount of calcium that enters the cell during low concentrations of calcium. However, along with limiting the entry of calcium into the mitochondrial matrix, it functions alongside MCU to keep the accumulated calcium inside the matrix of the mitochondria, and promotes ion specificity by preventing aberrant loading of transition metals into the mitochondria.
438:
sequestered there is reduced calcium; however, whenever MICU1 is sequestered and MICU2 is activated, normal calcium flow. It is also shown that all three, MCU, MICU1, and MICU2 are part of a single complex, the mitochondrial calcium uniporter complex resumes. Research using a CRISPR/Cas9 technique has found that MICU1 and MICU2 play other roles as well. They are essential for cell growth, cell invasion, and cell replication.
428:
The mitochondrial calcium uptake 1 (MICU1) is a single pass membrane protein, it contains 2 binding domains. This protein was first discovered before the MCU by only a few months. MICU1 was used as a bait to figure out what the core of the mitochondrial calcium uniporter was. Once both MICU1 and MCU
437:
Mitochondrial calcium uptake 2 (MICU2) is another intermitochondrial membrane protein. It works alongside MICU1 and contains roughly 25% of the same DNA sequence. MICU2 works with MICU1 and MCU to reduce the amount of calcium coming into the matrix. It is shown that when both MICU1 and MICU2 are
377:
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
405:) 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.
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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
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583:"Oxygen-bridged dinuclear ruthenium amine complex specifically inhibits Ca2+ uptake into mitochondria in vitro and in situ in single cardiac myocytes"
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Broekemeier KM, Krebsbach RJ, Pfeiffer DR (October 1994). "Inhibition of the mitochondrial Ca2+ uniporter by pure and impure ruthenium red".
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are typical reagents used to experimentally block the MCU to study its properties and role in mitochondrial signaling.
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491:"The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications"
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Monteith AJ, Miller JM, Beavers WN, Maloney KN, Seifert EL, Hajnoczky G, et al. (December 2021).
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Wettmarshausen J, Goh V, Huang KT, Arduino DM, Tripathi U, Leimpek A, et al. (November 2018).
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The MCU is one of the primary sources of mitochondria uptake of calcium, and flow is dependent on
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624:"MICU1 imparts the mitochondrial uniporter with the ability to discriminate between Ca and Mn"
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Kamer KJ, Sancak Y, Fomina Y, Meisel JD, Chaudhuri D, Grabarek Z, et al. (August 2018).
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Matlib MA, Zhou Z, Knight S, Ahmed S, Choi KM, Krause-Bauer J, et al. (April 1998).
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366:, which together with the MCU make up the mitochondrial calcium uniporter complex.
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733:"Mitochondrial calcium uniporter affects neutrophil bactericidal activity during
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456:"MCU - Calcium uniporter protein, mitochondrial precursor - Homo sapiens (Human)"
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Proceedings of the
National Academy of Sciences of the United States of America
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393:(ER), at contact sites, which contains stores of cellular calcium ions for
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683:"MICU1 Confers Protection from MCU-Dependent Manganese Toxicity"
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587:The Journal of Biological Chemistry
540:Molecular and Cellular Biochemistry
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489:Marchi S, Pinton P (March 2014).
358:. Its activity is regulated by
337:mitochondrial calcium uniporter
181:Mitochondrial calcium uniporter
24:Mitochondrial calcium uniporter
1:
118:Available protein structures:
791:Genes on human chromosome 10
702:10.1016/j.celrep.2018.10.037
507:10.1113/jphysiol.2013.268235
375:inner mitochondrial membrane
202:C10orf42, CCDC109A, FLJ46135
343:that allows the passage of
16:Group of transport proteins
822:
796:Transmembrane transporters
495:The Journal of Physiology
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600:10.1074/jbc.273.17.10223
380:sodium-calcium exchanger
649:10.1073/pnas.1807811115
385:The MCU has a very low
741:Infection and Immunity
735:Staphylococcus aureus
391:endoplasmic reticulum
341:transmembrane protein
753:10.1128/IAI.00551-21
462:. UniProt Consortium
696:(6): 1425–1435.e7.
640:2018PNAS..115E7960K
634:(34): E7960–E7969.
593:(17): 10223–10231.
552:10.1007/bf00944201
399:1,4,5-triphosphate
397:. The presence of
371:membrane potential
801:Calcium signaling
747:(2): IAI0055121.
395:calcium signaling
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167:structure summary
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79:OPM superfamily
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546:(1): 33–40.
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356:mitochondria
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199:Alt. symbols
18:
460:UniProt.org
339:(MCU) is a
314:Swiss-model
186:Identifiers
91:OPM protein
29:Identifiers
785:Categories
737:infection"
466:2016-02-24
442:References
310:Structures
305:Search for
279:Other data
130:structures
103:Membranome
261:NM_138357
208:NCBI gene
60:IPR018782
771:34871043
718:53209158
710:30403999
668:30082385
525:24366263
387:affinity
324:InterPro
147:RCSB PDB
55:InterPro
762:8853686
659:6112746
636:Bibcode
609:9553073
560:7531818
516:3948548
373:of the
352:cytosol
345:calcium
320:Domains
290:Chr. 10
268:UniProt
48:PF04678
769:
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708:
666:
656:
607:
568:516473
566:
558:
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273:Q8NE86
256:RefSeq
249:Q8NE86
237:614197
191:Symbol
162:PDBsum
136:
126:
72:1.A.77
34:Symbol
714:S2CID
686:(PDF)
564:S2CID
433:MICU2
424:MICU1
413:Ru360
364:MICU2
360:MICU1
354:into
285:Locus
225:23526
213:90550
767:PMID
706:PMID
664:PMID
605:PMID
556:PMID
521:PMID
411:and
362:and
348:ions
335:The
232:OMIM
220:HGNC
155:PDBj
151:PDBe
134:ECOD
124:Pfam
96:6dnf
67:TCDB
43:Pfam
757:PMC
749:doi
698:doi
654:PMC
644:doi
632:115
595:doi
591:273
548:doi
544:139
511:PMC
503:doi
499:592
401:(IP
294:222
244:PDB
194:MCU
142:PDB
108:216
84:486
37:MCU
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