Mitochondrial carrier
Encyclopedia
Mitochondrial carriers are proteins from the solute carrier family
which transfers molecules across the membranes of the mitochondria.
s, which are involved in energy transfer, have been found in the inner membranes of mitochondria
and other eukaryotic organelles such as the peroxisome
. Such proteins include: ADP
, ATP
carrier protein (ADP/ATP translocase); 2-oxoglutarate/malate
carrier protein; phosphate
carrier protein; tricarboxylate transport protein (or citrate
transport protein); Graves disease carrier protein; yeast mitochondrial proteins MRS3 and MRS4; yeast mitochondrial FAD carrier protein; and many others.
and there are six definable transmembrane segments in each carrier. All carriers also contain a common sequence, referred to as the MCF motif, in each repeated region, with some variation in one or two signature sequences.
Amongst the members of the mitochondrial carrier family that have been identified, it is the ADP/ATP carrier (AAC) that is responsible for importing ADP into the mitochondria and exporting ATP out of the mitochondria and into the cytosol following synthesis. The AAC is an integral membrane protein
that is synthesised lacking a cleavable presequence, but instead contains internal targeting information. It forms a dimer of two identical subunits and consists of a basket shaped structure with six transmembrane helices that are tilted with respect to the membrane, 3 of them kinked at the level of proline
residues.
Solute carrier family
The solute carrier group of membrane transport proteins include over 300 members organized into 51 families. The SLC gene nomenclature system was originally proposed by the Human Genome Organization and is the basis for the official HUGO names of the genes that encode these transporters...
which transfers molecules across the membranes of the mitochondria.
Function
A variety of substrate carrier proteinCarrier protein
Carrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is they exist within and span the membrane across which they transport substances. The...
s, which are involved in energy transfer, have been found in the inner membranes of mitochondria
Inner mitochondrial membrane
The mitochondrial inner membrane forms internal compartments known as cristae, which allow greater space for the proteins such as cytochromes to function properly and efficiently. The electron transport chain is located on the inner membrane of the mitochondria...
and other eukaryotic organelles such as the peroxisome
Peroxisome
Peroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...
. Such proteins include: ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
, ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
carrier protein (ADP/ATP translocase); 2-oxoglutarate/malate
Malate
Malate is the ionized form of malic acid. It is an important chemical compound in biochemistry. In the C4 carbon fixation process, malate is a source of CO2 in the Calvin cycle....
carrier protein; phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
carrier protein; tricarboxylate transport protein (or citrate
Citrate
A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...
transport protein); Graves disease carrier protein; yeast mitochondrial proteins MRS3 and MRS4; yeast mitochondrial FAD carrier protein; and many others.
Structure
All mitochondrial carriers are encoded by nuclear genes. Most contain a primary structure exhibiting regions of 100 homologous amino acid repeats, the N and C termini face the intermembrane spaceIntermembrane space
The intermembrane space also known as IMS is the region between the inner membrane and the outer membrane of a mitochondrion or a chloroplast. The main function of the intermembrane space is oxidative phosphorylation....
and there are six definable transmembrane segments in each carrier. All carriers also contain a common sequence, referred to as the MCF motif, in each repeated region, with some variation in one or two signature sequences.
Amongst the members of the mitochondrial carrier family that have been identified, it is the ADP/ATP carrier (AAC) that is responsible for importing ADP into the mitochondria and exporting ATP out of the mitochondria and into the cytosol following synthesis. The AAC is an integral membrane protein
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
that is synthesised lacking a cleavable presequence, but instead contains internal targeting information. It forms a dimer of two identical subunits and consists of a basket shaped structure with six transmembrane helices that are tilted with respect to the membrane, 3 of them kinked at the level of proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
residues.
Substrates
Examples of transported compounds include:- citrateCitrateA citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...
- - ornithineOrnithineOrnithine is an amino acid that plays a role in the urea cycle.-Role in urea cycle:L-Ornithine is one of the products of the action of the enzyme arginase on L-arginine, creating urea. Therefore, ornithine is a central part of the urea cycle, which allows for the disposal of excess nitrogen....
- , - phosphatePhosphateA phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
- , , , - adenine nucleotide - , , ,
- dicarboxylate -
- oxoglutarate -
- glutamate -
Examples
Human proteins containing this domain include:- HDMCP, LOC153328, MCART1, MCART2, MCART6, MTCH1MTCH1Mitochondrial carrier homolog 1 is a protein that in humans is encoded by the MTCH1 gene.-Further reading:...
, MTCH2MTCH2Mitochondrial carrier homolog 2 also known as MTCH2 is a protein which in humans is encoded by the MTCH2 gene.... - UCP1ThermogeninThermogenin is an uncoupling protein found in the mitochondria of brown adipose tissue . It is used to generate heat by non-shivering thermogenesis...
, UCP2UCP2Mitochondrial uncoupling protein 2 is a protein that in humans is encoded by the UCP2 gene.-Further reading:...
, UCP3UCP3Mitochondrial uncoupling protein 3 is a protein that in humans is encoded by the UCP3 gene.-Function:Mitochondrial uncoupling proteins are members of the larger family of mitochondrial anion carrier proteins . UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as... - SLC25A1SLC25A1Tricarboxylate transport protein, mitochondrial is a protein that in humans is encoded by the SLC25A1 gene.-Further reading:...
, SLC25A3SLC25A3Phosphate carrier protein, mitochondrial is a protein that in humans is encoded by the SLC25A3 gene.-Further reading:...
, SLC25A4SLC25A4ADP/ATP translocase 1 is an enzyme that in humans is encoded by the SLC25A4 gene.-Interactions:SLC25A4 has been shown to interact with Bcl-2-associated X protein.-Further reading:...
, SLC25A5, SLC25A6SLC25A6ADP/ATP translocase 3 also known as solute carrier family 25 member 6 is a protein that in humans is encoded by the SLC25A6 gene.Identical copies of this gene reside on the pseudoautosomal regions of the X and Y chromosomes....
, SLC25A10SLC25A10Mitochondrial dicarboxylate carrier is a protein that in humans is encoded by the SLC25A10 gene.-Further reading:...
, SLC25A11SLC25A11Mitochondrial 2-oxoglutarate/malate carrier protein is a protein that in humans is encoded by the SLC25A11 gene.-Further reading:...
, SLC25A12SLC25A12Calcium-binding mitochondrial carrier protein Aralar1 is a protein that in humans is encoded by the SLC25A12 gene.-Further reading:...
, SLC25A13, SLC25A14SLC25A14Brain mitochondrial carrier protein 1 is a protein that in humans is encoded by the SLC25A14 gene.-Further reading:...
, SLC25A16, SLC25A17SLC25A17Peroxisomal membrane protein PMP34 is a protein that in humans is encoded by the SLC25A17 gene.-Further reading:...
, SLC25A18, SLC25A19SLC25A19Mitochondrial thiamine pyrophosphate carrier is a protein that in humans is encoded by the SLC25A19 gene.-External links:* *...
, SLC25A21, SLC25A22, SLC25A23, SLC25A24, SLC25A25, SLC25A26, SLC25A27SLC25A27Mitochondrial uncoupling protein 4 is a protein that in humans is encoded by the SLC25A27 gene.-Further reading:...
, SLC25A28, SLC25A29, SLC25A30, SLC25A31SLC25A31ADP/ATP translocase 4 is an enzyme that in humans is encoded by the SLC25A31 gene.-Further reading:...
, SLC25A32, SLC25A33, SLC25A34, SLC25A35, SLC25A36, SLC25A37SLC25A37Mitoferrin-1 is a protein that in humans is encoded by the SLC25A37 gene.-Further reading:...
, SLC25A38SLC25A38SLC25A38 is a human gene....
, SLC25A39SLC25A39Solute carrier family 25 member 39 is a protein that in humans is encoded by the SLC25A39 gene.-Further reading:...
, SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, SLC25A46