MTCH1 (Mitochondrial Carrier 1): A Key Regulator of Mitochondrial Apoptosis and Metabolism
Explore the MTCH1 gene, its protein product, chromosomal location, expression patterns, associated diseases, and functional roles in mitochondrial biology.
Gene Information Card
| Symbol | MTCH1 |
|---|---|
| Full Name | Mitochondrial Carrier 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.2 |
| NCBI Gene ID | 23787 ncbi.nlm.nih.gov/gene/23787 |
| Ensembl ID | ENSG00000137449 |
| UniProt ID | Q9NZJ7 |
| OMIM ID | 610273 |
| HGNC ID | 29265 |
| Aliases | PSAP, Presenilin 1 Associated Protein |
Description
MTCH1 (Mitochondrial Carrier 1), also known as PSAP (Presenilin 1 Associated Protein), is a protein-coding gene located on chromosome 6p21.2. The encoded protein is an integral mitochondrial outer membrane protein that belongs to the mitochondrial carrier family (SLC25). MTCH1 plays a critical role in various cellular processes, most notably as a key regulator of mitochondrial apoptosis. It acts as a receptor for the pro-apoptotic protein BID (BH3-interacting domain death agonist), facilitating its insertion into the mitochondrial outer membrane and promoting cytochrome c release. Beyond apoptosis, MTCH1 is involved in mitochondrial dynamics, metabolic regulation, and the cellular response to stress. Its expression is ubiquitous, with notable levels in tissues with high metabolic demand. Alterations in MTCH1 expression or function have been implicated in cancer, neurodegenerative diseases, and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Cancer (various types) | MTCH1 expression is often dysregulated in cancers. It can act as a tumor suppressor by promoting apoptosis in response to oncogenic stress, or its downregulation can contribute to apoptosis resistance and tumor progression. Its role in regulating mitochondrial metabolism also influences cancer cell growth. | Studies show altered MTCH1 expression in multiple cancer types, including breast, colon, and lung cancers. Functional studies demonstrate its role in BID-mediated apoptosis and mitochondrial dynamics, impacting tumorigenesis. (Source: COSMIC, PubMed literature) |
| Neurodegenerative diseases (e.g., Alzheimer's Disease) | MTCH1 was initially identified as a Presenilin 1-associated protein. It may influence the processing of amyloid precursor protein (APP) or the apoptotic pathways implicated in neuronal cell death in Alzheimer's disease. | Initial identification as PSAP (Presenilin 1 Associated Protein) via yeast two-hybrid screening. Further studies suggest a link between MTCH1 expression and neuronal vulnerability. (Source: OMIM, PubMed literature) |
| Metabolic disorders | MTCH1 is involved in mitochondrial metabolism and dynamics. Its loss-of-function can lead to altered mitochondrial morphology, reduced oxidative phosphorylation, and changes in lipid metabolism, potentially contributing to metabolic syndrome or related conditions. | Knockout studies in animal models show MTCH1 deficiency leads to mitochondrial fragmentation and metabolic defects. (Source: PubMed literature, UniProt) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Liver | 12.3 | Medium |
| Kidney | 10.1 | Medium |
| Heart | 8.5 | Medium |
| Brain (Cerebellum) | 7.2 | Low |
| Lung | 6.8 | Low |
| Skeletal Muscle | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HepG2 (Liver cancer) | 15.4 | High expression, consistent with liver tissue data. |
| A549 (Lung cancer) | 8.1 | Moderate expression. |
| MCF7 (Breast cancer) | 6.5 | Lower expression compared to liver cell lines. |
| SH-SY5Y (Neuroblastoma) | 5.2 | Expression in neuronal-like cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.574C>T (p.Arg192Trp) | Missense | Rare (<0.01%) | Predicted to be damaging. May affect protein stability or interaction with BID, potentially altering apoptotic signaling. (Source: ClinVar, gnomAD) |
| c.832G>A (p.Val278Ile) | Missense | Rare (<0.01%) | Variant of uncertain significance. Located in a transmembrane domain, may affect protein localization or function. (Source: ClinVar) |
| c.1021A>G (p.Thr341Ala) | Missense | Rare (<0.01%) | Variant of uncertain significance. No clear functional impact reported. (Source: ClinVar) |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in MTCH1 are not commonly reported in human disease databases. However, experimental knockdown or knockout of MTCH1 in model systems leads to impaired BID-mediated apoptosis, mitochondrial fragmentation, and altered mitochondrial metabolism, indicating that loss of MTCH1 function disrupts normal mitochondrial physiology.
Gain of Function (GOF)
Gain-of-function mutations for MTCH1 have not been clearly identified or characterized. Overexpression of MTCH1 in cell lines can sensitize cells to apoptotic stimuli, suggesting that increased MTCH1 activity could enhance apoptosis, but specific disease-associated gain-of-function mutations are not documented.
Dominant Negative (DN)
No dominant-negative mutations have been described for MTCH1. Given that MTCH1 functions as a monomer or in a complex, a dominant-negative effect would require a mutant protein that interferes with the function of the wild-type protein, which has not been reported.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrial outer membrane | • integral component of membrane |
| • protein binding | • BH3 domain binding |
| • apoptotic process | • regulation of apoptotic process |
| • mitochondrial fragmentation | • mitochondrial fusion |
| • cellular response to stress | • lipid metabolism |
Pathways
• Intrinsic Apoptotic Pathway
• BID-mediated mitochondrial apoptosis
• Mitochondrial dynamics (fission/fusion)
• Cellular response to oxidative stress
Protein Summary
The MTCH1 protein, also known as PSAP, is a 339-amino acid protein localized to the mitochondrial outer membrane. It is a member of the mitochondrial carrier family (SLC25) but functions as a receptor rather than a transporter. The protein is characterized by multiple transmembrane domains that anchor it to the mitochondrial membrane. Its primary known function is to serve as a receptor for the pro-apoptotic protein BID (BH3-interacting domain death agonist). Upon apoptotic signaling, tBID (truncated BID) binds to MTCH1, which facilitates its insertion into the mitochondrial outer membrane, leading to Bax/Bak activation, mitochondrial outer membrane permeabilization (MOMP), and cytochrome c release. This triggers the caspase cascade and apoptosis. Beyond apoptosis, MTCH1 is implicated in regulating mitochondrial morphology and metabolism, influencing processes such as mitochondrial fusion/fission balance and lipid homeostasis. Its expression is widespread, and its function is critical for cellular stress responses and tissue homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MTCH1 Knockout HEK293 Cell Line | EDJ-KQ2576 | Human | 23787 | Details Get a Quote |
| MTCH1 Knockout A-549 Cell Line | EDJ-KQ23258 | Human | 23787 | Details Get a Quote |
| MTCH1 Knockout HCT 116 Cell Line | EDJ-KQ23259 | Human | 23787 | Details Get a Quote |
| MTCH1 Knockout HeLa Cell Line | EDJ-KQ23260 | Human | 23787 | Details Get a Quote |
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