MTCH1

Mitochondrial carrier homolog 1 (MTCH1), also referred to as presenilin 1-associated protein (PSAP), is a protein that in humans is encoded by the MTCH1 gene on chromosome 6.^[5][6][7] MTCH1 is a proapoptotic mitochondrial protein potentially involved in Alzheimer's disease (AD).^[6][7][8]

MTCH1
Identifiers
Aliases	MTCH1, CGI-64, PIG60, PSAP, SLC25A49, mitochondrial carrier 1
External IDs	OMIM: 610449; MGI: 1929261; HomoloGene: 22807; GeneCards: MTCH1; OMA:MTCH1 - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p21.2 Start 36,965,807 bp[1] End 36,986,298 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 A3.3 Start 29,551,046 bp[2] End 29,566,908 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell Brodmann area 23 middle temporal gyrus inferior olivary nucleus pancreatic ductal cell dorsal motor nucleus of vagus nerve entorhinal cortex corpus epididymis Epithelium of choroid plexus superior frontal gyrus Top expressed in saccule dentate gyrus of hippocampal formation granule cell vestibular membrane of cochlear duct otic placode otic vesicle superior frontal gyrus dorsomedial hypothalamic nucleus lateral septal nucleus molar ventricular zone More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component integral component of membrane intracellular anatomical structure mitochondrial inner membrane mitochondrion membrane Biological process regulation of signal transduction apoptotic process positive regulation of apoptotic process neuronal ion channel clustering activation of cysteine-type endopeptidase activity involved in apoptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23787 56462 Ensembl ENSG00000137409 ENSMUSG00000024012 UniProt Q9NZJ7 Q791T5 RefSeq (mRNA) NM_001271641 NM_014341 NM_019880 NM_001347335 NM_001357762 NM_001357763 RefSeq (protein) NP_001258570 NP_055156 NP_001334264 NP_063933 NP_001344691 NP_001344692 Location (UCSC) Chr 6: 36.97 – 36.99 Mb Chr 17: 29.55 – 29.57 Mb PubMed search [3] [4]
Wikidata
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Structure

The protein encoded by this gene is named for its structural resemblance to the members of the mitochondrial carrier protein family.^[5][7] The MTCH1 gene contains 12 exons and produces four isoforms. These isoforms arise from alternative splicing of exon 8 and two potential start codons, which results in the deletion of 17 amino acid residues in the hydrophilic loop between two transmembrane domains of some isoforms.^[9][10] Though they differ in sequence and length, the four isoforms still share a similar topological structure, including six transmembrane domains, one of which is responsible for localization to the outer mitochondrial membrane (OMM), and two N-terminal apoptotic domains. As a result, all four isoforms retain these apoptotic domains and mitochondrial localization, both of which are required for the protein's proapoptotic function.^[7][9][10]

Function

MTCH1 is a proapoptotic protein that localizes to the OMM and induces apoptosis independently of BAX and BAK.^[6][7] One possible mechanism proposes that its interactions with the mitochondrial permeability transition pore (MPTP) complex leads to depolarization of the mitochondrial membrane, release of cytochrome C, and activation of caspase-3.^[5][7] Expression of this protein is observed in 16 different tissue types, indicating that the protein may serve a housekeeping function.^[10]

Clinical Significance

MTCH1 may be associated with AD and other neurodegenerative and neuroinflammatory diseases through its close interaction with presenilin.^[5][8] However, more research is required to confirm its clinical involvement.^[8]

Interactions

MTCH1 has been shown to interact with PS1.^[5]