MICU1

This gene encodes an essential regulator of mitochondrial Ca2+ uptake under basal conditions. The encoded protein interacts with the mitochondrial calcium uniporter, a mitochondrial inner membrane Ca2+ channel, and is essential in preventing mitochondrial Ca2+ overload, which can cause excessive production of reactive oxygen species and cell stress. Alternatively spliced transcript variants encoding different isoforms have been described.

Full Name

Mitochondrial Calcium Uptake 1

Alternative Names

Mitochondrial Calcium Uptake 1; Calcium-Binding Atopy-Related Autoantigen 1; Atopy-Related Autoantigen CALC; Ara CALC; CBARA1; CALC;

Function

Key regulator of mitochondrial calcium uniporter (MCU) that senses calcium level via its EF-hand domains (PubMed:20693986, PubMed:23101630, PubMed:23747253, PubMed:24313810, PubMed:24332854, PubMed:24503055, PubMed:24560927, PubMed:26341627, PubMed:26903221, PubMed:27099988).

MICU1 and MICU2 form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium. MICU1 acts both as an activator or inhibitor of mitochondrial calcium uptake (PubMed:26903221).

Acts as a gatekeeper of MCU at low concentration of calcium, preventing channel opening (PubMed:26903221).

Enhances MCU opening at high calcium concentration, allowing a rapid response of mitochondria to calcium signals generated in the cytoplasm (PubMed:24560927, PubMed:26903221).

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

Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (PubMed:16002733).

Biological Process

Calcium import into the mitochondrion Source: ComplexPortal
Calcium ion import Source: UniProtKB
Defense response Source: ProtInc
Mitochondrial calcium ion homeostasis Source: ComplexPortal
Mitochondrial calcium ion transmembrane transport Source: UniProtKB
Positive regulation of mitochondrial calcium ion concentration Source: UniProtKB
Protein homooligomerization Source: UniProtKB
Regulation of cellular hyperosmotic salinity response Source: UniProtKB

Cellular Location

Mitochondrion
Mitochondrion inner membrane
Mitochondrion intermembrane space

Involvement in disease

Myopathy with extrapyramidal signs (MPXPS):
An autosomal recessive disorder characterized by early-onset proximal muscle weakness with a static course and moderately to grossly elevated serum creatine kinase levels accompanied by learning difficulties. Most patients develop subtle extrapyramidal motor signs that progress to a debilitating disorder of involuntary movement with variable features, including chorea, tremor, dystonic posturing and orofacial dyskinesia. Additional variable features include ataxia, microcephaly, ophthalmoplegia, ptosis, optic atrophy and axonal peripheral neuropathy.
An homozygous partial MICU1 deletion is responsible for a disorder manifesting in childhood with fatigue, lethargy and muscle weakness. The disease is caused by variants affecting the gene represented in this entry.

Topology

Helical: 34-52
Mitochondrial intermembrane: 53-476