Solute carrier family 25 member 46 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, res ...

that in humans is encoded by the ''SLC25A46''

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 b ...

. This protein is a member of the SLC25 mitochondrial solute carrier

family Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its members and of society. Idea ...

. It is a

transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...

located in the mitochondrial outer membrane involved in

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...

transfer from the endoplasmic reticulum (ER) to mitochondria.

Mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...

s in this gene result in neuropathy and optic atrophy.

Structure

The ''SLC25A46'' gene is located on the q arm of

chromosome 5 Chromosome 5 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 5 spans about 181 million base pairs (the building blocks of DNA) and represents almost 6% of the total DNA in cells. C ...

in position 22.1 and spans 27,039 base pairs. The gene produces a 46.2 kDa protein composed of 418 amino acids. This gene has 8 exons and encodes a multi-pass

integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a sign ...

localized to the mitochondrial outer membrane.

Function

The encoded protein is an orphan transporter involved in lipid transfer from the endoplasmic reticulum to mitochondria. It promotes mitochondrial fission and prevents the formation of hyperfilamentous mitochondria. This protein forms a

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

with mitofilin (

IMMT Mitochondrial inner membrane protein is a protein that in humans is encoded by the ''IMMT'' gene.) ''IMMT'' encodes an inner mitochondrial membrane (IMM) protein in the nucleus. It is posttranslational transported to the IMM. Mic60/Mitofilin (enc ...

) on the inner mitochondrial membrane, independent of

MFN2 Mitofusin-2 is a protein that in humans is encoded by the ''MFN2'' gene. Mitofusins are GTPases embedded in the outer membrane of the mitochondria. In mammals MFN1 and MFN2 are essential for mitochondrial fusion. In addition to the mitofusins, OP ...

Clinical Significance

Mutations in the ''SLC25A46'' gene, inherited in an autosomal recessive manner, cause type 6B hereditary motor and sensory neuropathy. Symptoms include early-onset optic atrophy, progressive visual loss, and peripheral sensorimotor neuropathy manifesting as

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...

al Charcot-Marie-Tooth disease, with variable age at onset and severity. Overexpression of this protein causes mitochondrial fragmentation while knockdown of this protein causes mitochondrial hyperfusion and hyperfilamentous mitochondria due to decreased mitochondrial fission. Loss of this gene also has many other effects: premature cellular senescence, impaired

cellular respiration Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor such as oxygen to produce large amounts of energy, to drive the bulk production of ATP. Cellular respiration may be des ...

, destabilization of the MICOS (mitochondrial contact site and cristae organizing system) complex, loss of and shortened cristae, altered ER

morphology Morphology, from the Greek and meaning "study of shape", may refer to: Disciplines * Morphology (archaeology), study of the shapes or forms of artifacts * Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies ...

, impaired

cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular dire ...

, and changes in mitochondrial phospholipid composition.

Interactions

This protein interacts with

, a component of the MICOS complex, along with other components of this complex and components of an ER membrane protein complex involved in transferring lipids to mitochondria. Additionally, this protein interacts with

SLC7A8 Large neutral amino acids transporter small subunit 2 is a protein that in humans is encoded by the ''SLC7A8'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity. ...

SLC10A1 Sodium/bile acid cotransporter also known as the Na+-taurocholate cotransporting polypeptide (NTCP) or liver bile acid transporter (LBAT) is a protein that in humans is encoded by the ''SLC10A1'' (solute carrier family 10 member 1) gene. Struct ...

, SLC10A6,

FHL3 Four and a half LIM domains protein 3 is a protein that in humans is encoded by the ''FHL3'' gene. LIM proteins are defined by the possession of a highly conserved double zinc finger motif called the LIM domain. upplied by OMIMref name="entrez"/ ...

FUNDC1 FUN14 domain containing 1 is a protein that in humans is encoded by the FUNDC1 gene. Model organisms Model organisms have been used in the study of FUNDC1 function. A conditional knockout mouse line, called ''Fundc1tm1a(KOMP)Wtsi'' was generate ...

, linc01142, LEPROTL1, ODF4, VMA21,

MFSD14B Major facilitator superfamily The major facilitator superfamily (MFS) is a superfamily of membrane transport proteins that facilitate movement of small solutes across cell membranes in response to chemiosmotic gradients. Function The major fac ...

, PQLC1, HSD17B11,

REEP2 Receptor expression-enhancing protein 2 is a protein that in humans is encoded by the ''REEP2'' gene. Function The protein encoded by REEP2 belongs to a family of proteins with receptor enhancing expression capabilities, including possible enh ...

, REEP4, and TOMM22. This protein possibly interacts with

OPA1 Dynamin-like 120 kDa protein, mitochondrial is a protein that in humans is encoded by the ''OPA1'' gene. This protein regulates mitochondrial fusion and cristae structure in the inner mitochondrial membrane (IMM) and contributes to ATP synthesis an ...

and

Structure

Function

Clinical Significance

Interactions

References

Further reading