Mitochondrial carrier homolog 1 (MTCH1), also referred to as presenilin 1-associated protein (PSAP), is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''MTCH1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

on chromosome 6. MTCH1 is a

proapoptotic Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes inclu ...

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

l protein potentially involved in

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

(AD).

Structure

The protein encoded by this gene is named for its structural resemblance to the members of the

mitochondrial carrier Mitochondrial carriers are proteins from solute carrier family 25 which transfer molecules across the membranes of the mitochondria. Mitochondrial carriers are also classified in thTransporter Classification Database The Mitochondrial Carrier (M ...

protein family. The ''MTCH1'' gene contains 12

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s and produces four

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

s. These isoforms arise from

alternative splicing Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...

of exon 8 and two potential

start codon The start codon is the first codon of a messenger RNA (mRNA) transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and Archaea and a N-formylmethionine (fMet) in bacteria, mitochondria and plastids. The ...

s, which results in the deletion of 17

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

residues in the hydrophilic loop between two

transmembrane domain A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bil ...

s of some isoforms. 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 Localization or localisation may refer to: Biology * Localization of function, locating psychological functions in the brain or nervous system; see Linguistic intelligence * Localization of sensation, ability to tell what part of the body is a ...

to the

outer mitochondrial membrane A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used t ...

(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.

Function

MTCH1 is a proapoptotic protein that localizes to the OMM and induces apoptosis independently of BAX and BAK. One possible mechanism proposes that its interactions with the

mitochondrial permeability transition pore The mitochondrial permeability transition pore (mPTP or MPTP; also referred to as PTP, mTP or MTP) is a protein that is formed in the inner membrane of the mitochondria under certain pathological conditions such as traumatic brain injury and stroke ...

(MPTP) complex leads to

depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...

of the mitochondrial membrane, release of

cytochrome C The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apoptosis. Cytochrome c is hig ...

, and activation of

caspase-3 Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the ''CASP3'' gene. ''CASP3'' orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also p ...

. Expression of this protein is observed in 16 different tissue types, indicating that the protein may serve a

housekeeping Housekeeping is the management and routine support activities of running an organised physical institution occupied or used by people, like a house, ship, hospital or factory, such as tidying, cleaning, cooking, routine maintenance, shopping, ...

function.

Clinical Significance

MTCH1 may be associated with AD and other

neurodegenerative A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

and neuro inflammatory

disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

s through its close interaction with

presenilin Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset ...

. However, more research is required to confirm its clinical involvement.

Interactions

MTCH1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with PS1.

Structure

Function

Clinical Significance

Interactions

References

Further reading