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
AliasesMTCH1, CGI-64, PIG60, PSAP, SLC25A49, mitochondrial carrier 1
External IDsOMIM: 610449 MGI: 1929261 HomoloGene: 22807 GeneCards: MTCH1
Orthologs
SpeciesHumanMouse
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 MbChr 17: 29.55 – 29.57 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

References

  1. GRCh38: Ensembl release 89: ENSG00000137409 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000024012 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Xu X, Shi YC, Gao W, Mao G, Zhao G, Agrawal S, Chisolm GM, Sui D, Cui MZ (Dec 2002). "The novel presenilin-1-associated protein is a proapoptotic mitochondrial protein". J Biol Chem. 277 (50): 48913–48922. doi:10.1074/jbc.M209613200. PMID 12377771.
  6. "Entrez Gene: MTCH1 mitochondrial carrier homolog 1 (C. elegans)".
  7. Lamarca, V; Marzo, I; Sanz-Clemente, A; Carrodeguas, JA (May 2008). "Exposure of any of two proapoptotic domains of presenilin 1-associated protein/mitochondrial carrier homolog 1 on the surface of mitochondria is sufficient for induction of apoptosis in a Bax/Bak-independent manner". European Journal of Cell Biology. 87 (5): 325–34. doi:10.1016/j.ejcb.2008.02.004. PMID 18375015.
  8. Vural, B; Sehitoğlu, E; Cavuş, F; Yalçınkaya, N; Haytural, H; Küçükerden, M; Ulusoy, C; Uğurel, E; Turan, S; Bulut, L; Türkoğlu, R; Shugaiv, E; Kürtüncü, M; Atakan, S; Güre, AO; Gül, A; Eraksoy, M; Akman-Demir, G; Tüzün, E (15 October 2013). "Mitochondrial carrier homolog 1 (Mtch1) antibodies in neuro-Behçet's disease". Journal of Neuroimmunology. 263 (1–2): 139–44. doi:10.1016/j.jneuroim.2013.08.007. hdl:11693/12552. PMID 24035008. S2CID 13300599.
  9. Mao, G; Tan, J; Gao, W; Shi, Y; Cui, MZ; Xu, X (April 2008). "Both the N-terminal fragment and the protein-protein interaction domain (PDZ domain) are required for the pro-apoptotic activity of presenilin-associated protein PSAP". Biochimica et Biophysica Acta (BBA) - General Subjects. 1780 (4): 696–708. doi:10.1016/j.bbagen.2008.01.013. PMC 3509497. PMID 18291114.
  10. Lamarca, V; Sanz-Clemente, A; Pérez-Pé, R; Martínez-Lorenzo, MJ; Halaihel, N; Muniesa, P; Carrodeguas, JA (October 2007). "Two isoforms of PSAP/MTCH1 share two proapoptotic domains and multiple internal signals for import into the mitochondrial outer membrane". American Journal of Physiology. Cell Physiology. 293 (4): C1347–61. doi:10.1152/ajpcell.00431.2006. PMID 17670888. S2CID 43241603.

Further reading

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