MCU

This gene encodes a calcium transporter that localizes to the mitochondrial inner membrane. The encoded protein interacts with mitochondrial calcium uptake 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

Mitochondrial Calcium Uniporter

Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria (PubMed:21685888, PubMed:21685886, PubMed:23101630, PubMed:22904319, PubMed:23178883, PubMed:22829870, PubMed:22822213, PubMed:24332854, PubMed:23755363, PubMed:26341627).

Constitutes the pore-forming and calcium-conducting subunit of the uniporter complex (uniplex) (PubMed:23755363).

Activity is regulated by MICU1 and MICU2. At low Ca2+ levels MCU activity is down-regulated by MICU1 and MICU2; at higher Ca2+ levels MICU1 increases MCU activity (PubMed:24560927, PubMed:26903221).

Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes (PubMed:22822213).

While dispensable for baseline homeostatic cardiac function, acts as a key regulator of short-term mitochondrial calcium loading underlying a 'fight-or-flight' response during acute stress: acts by mediating a rapid increase of mitochondrial calcium in pacemaker cells (PubMed:25603276).

participates in mitochondrial permeability transition during ischemia-reperfusion injury (By similarity).

Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319, PubMed:22829870).

Mitochondrial calcium uptake in skeletal muscle cells is involved in muscle size in adults (By similarity).

Regulates synaptic vesicle endocytosis kinetics in central nerve terminal (By similarity).

Involved in antigen processing and presentation (By similarity).

Actin filament reorganization Source: CACAO
Calcium import into the mitochondrion Source: MGI
Calcium-mediated signaling Source: UniProtKB
Glucose homeostasis Source: UniProtKB
Mitochondrial calcium ion homeostasis Source: ComplexPortal
Mitochondrial calcium ion transmembrane transport Source: UniProtKB
Positive regulation of insulin secretion Source: UniProtKB
Positive regulation of mitochondrial calcium ion concentration Source: UniProtKB
Positive regulation of mitochondrial fission Source: CACAO
Positive regulation of neutrophil chemotaxis Source: CACAO
Protein complex oligomerization Source: UniProtKB

Mitochondrion inner membrane

Mitochondrial matrix: 51-233
Helical: 234-256
Mitochondrial intermembrane: 257-265
Helical: 266-283
Mitochondrial matrix: 284-351

Phosphorylation by CaMK2 in heart leads to increased MCU current (PubMed:23051746, PubMed:25254481). The regulation of MCU by CaMK2 is however subject to discussion: another group was unable to reproduce these results (PubMed:25254480). Phosphorylated on tyrosines by PTK2B/PYK2, promoting oligomerization (PubMed:24800979).