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FLASH GENE
Symbol MCU contributors: mct - updated : 26-05-2016
HGNC name mitochondrial calcium uniporter
HGNC id 23526
Location 10q22.2      Physical location : -
Synonym name coiled-coil domain containing 109A
Synonym symbol(s) C10orf42, FLJ46135, CCDC109A
DNA
TYPE functioning gene
STRUCTURE 195.00 kb     8 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 2962 39 352 - 2015 25640838
CCDC109A
7 - 2899 - 330 - 2015 25640838
8 - 3239 - 302 - 2015 25640838
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N- terminal domain (NTD) of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY unknown/unspecified
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,membrane
    basic FUNCTION
  • is an essential component of the mitochondrial Ca(2+) uniporter
  • is essential for glucose-induced ATP increases in pancreatic beta-cells
  • crucial role of MICU1 and MCU in mitochondrial Ca(2+) uptake in pancreatic beta-cells and their involvement in the positive feedback required for sustained insulin secretion
  • encodes the pore-forming subunit of the uniporter channel
  • increases mitochondrial Ca(2+) levels following NMDA receptor activation, leading to increased mitochondrial membrane depolarization and excitotoxic cell death
  • MCU and the pathways regulating its expression as important determinants of excitotoxicity, which may represent therapeutic targets for excitotoxic disorders
  • plays an important role in mitochondrial matrix Ca(2+) influx
  • plays a critical role in breast cancer cell migration by regulating store-operated Ca2+ entry (SOCE
  • is a conserved Ca(2+) transporter at mitochondrial in eukaryotic cells
  • may be dispensable for homeostatic cardiac function but required to modulate Ca(2+)-dependent metabolism during acute stress
  • mitochondrial Ca(2+) uptake is primarily mediated by MCU
  • is a dedicated regulator of short-term mitochondrial Ca(2+) loading underlying a "fight-or-flight" response that acutely matches cardiac workload with ATP production
  • mitochondrial uniporter (MCU) is an ion channel that mediates Ca(2+) uptake into the matrix to regulate metabolism, cell death, and cytoplasmic Ca(2+) signaling
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MCU forms oligomers in the mitochondrial inner membrane, physically interacts with MICU1, and resides within a large molecular weight complex
  • MICU1 interacts with the uniporter pore-forming subunit MCU and sets a Ca2+ threshold for Ca2+m uptake without affecting the kinetic properties of MCU-mediated Ca2+ uptake
  • MICU1 inhibits the mitochondrial Ca2+ channel MCU under resting conditions
  • SMDT1 was required for the interaction of MCU with MICU1 and MICU2
  • SLC25A23 interacts with mitochondrial Ca(2+) uniporter (MCU) and MICU1 (CBARA1)
  • PDIA3 can regulate the expression of the mitochondrial calcium uniporter (MCU) and modulate mitochondrial calcium uptake
  • MCU interacts with VDAC1 and mediates VDAC1 overexpression-induced cell death in cerebellar granule neurons (CGNs)
  • MICU1 is a key regulator of the mitochondrial Ca(2+) uniporter (MCU) that together with the essential MCU regulator (SMDT1) forms the mitochondrial Ca(2+) channel
  • MCU channel activity is governed by matrix Ca(2+) concentration through SMDT1
  • SMDT1 second function is to maintain tight MICU1, MICU2 regulation of the MCU pore, a role that requires SMDT1 to bind MICU1 using its conserved C-terminal polyaspartate tail
  • MCUR1 binds to MCU and SMDT1 and function as a scaffold factor
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    known to mediate endoplasmic reticulum (ER) calcium release, as well as loss of ITPR2, necessary for mitochondrial calcium uptake, enable escape from oncogene-induced senescence (OIS)
    constitutional   deletion    
    vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Mcu(-/-) mice lack contractile responsiveness to acute beta-adrenergic receptor stimulation and in parallel are unable to activate mitochondrial dehydrogenases and display reduced bioenergetic reserve capacity
  • mitochondria from Mcu(-/-) mice lacked evidence for calcium-induced permeability transition pore (PTP) opening