2.A.29 The Mitochondrial Carrier (MC) Family
Permeases of the MC family (the human SLC25 family) possess six transmembrane α-helical spanners. The proteins are of fairly uniform size of about 300 residues. They arose by tandem intragenic triplication in which a genetic element encoding two spanners gave rise to one encoding six spanners (Palmieri 2012; Wang et al. 2016). This event may have occurred less than 2 billion years ago when mitochondria first developed their specialized endosymbiotic functions within eukaryotic cells. Members of the family are found exclusively in eukaryotic organelles although they are nuclearly encoded. Most are found in mitochondria, but some are found in peroxisomes of animals, in hydrogenosomes of anaerobic fungi, and in amyloplasts of plants. Members of the MC family are functional and structural monomers although early reports indicated that they are dimers (Bamber et al., 2006, 2007). Many of them preferentially catalyze the exchange of one solute for another (antiport). Fifteen paralogues of the MC family are encoded within the genome of Saccharomyces cerevisiae. Fifty have been identified in humans. 58 in A. thaliana and 35 in S. cerevisiae. The functions of many of the human homologues are unknown, but most of the yeast homologues have been functionally identified. Functional aspects have been reviewed by Palmieri (2004), Palmieri et al. (2006) and Plamieri and Pierri (2010). Diseases caused by defects of mitochondrial carriers are reviewed by Palmieri et al. (2008) and by Gutiérrez-Aguilar and Baines 2013. Residues involved in substrate binding in the middle of the transporter and gating have been identified and analyzed (Monné et al. 2013). The physiology and pathology of MCs has been reviewed (Palmieri and Monné 2016). Several of the 53 human mitochondrial SLC25 carriers are associated with genetic diseases (Rochette et al. 2020). In fact, mitochondrial transporter expression patterns
distinguish tumors from normal tissues and identify cancer subtypes with
different survival and metabolism (Wohlrab et al. 2022). Abnormal energy metabolism in mitochondria can be related to symptomatic severity in nemaline myopathy and may constitute a contributor to phenotypic variability (Tinklenberg et al. 2023).
Members of the mitochondrial carrier family are involved in transporting
keto acids, amino acids, nucleotides, inorganic ions and co-factors
across the mitochondrial inner membrane. The transporters are thought to
share the same structural fold, which consists of six trans-membrane
alpha-helices and three matrix helices, arranged with threefold
pseudo-symmetry. There are 53 MC homologues in humans. During the transport cycle two salt bridge networks on
either side of the central cavity might regulate access to a single
substrate binding site in an alternating fashion. In the case of
proton-substrate symporters, the substrate binding sites contain
negatively charged residues that are proposed to be involved in proton
transport (Kunji and Robinson, 2010). Wang et al. 2016 haved reviewed the structures and transport mechanisms of these porters. Some of the residues in the charged residue positions of the PX[DE]XX[KR] motifs are important for reasons other than forming salt bridges, probably for playing specific roles related to the substrate interaction-mediated conformational changes leading to the M-gate opening/closing (Miniero et al. 2022). Several intron positions are present in numerous MC sequences at the same specific points, of which some are 3-fold symmetry related (Monné et al. 2023).
The high resolution 3-D structure of the human homologue, the bovine ATP/ADP antiporter (TC #2.A.29.1.1), has been solved by x-ray crystallography to 2.2 Å resolution (Pebay-Peyroula et al., 2003; Klingenberg et al., 2008). The carrier was crystalized in complexation with the inhibitor, carboxyatractyloside. The six TMSs (with the N- and C-termini normally facing the cytoplasmic side of the membrane and the three hairpin loops of the repeat sequences facing the matrix) form a compact barrel domain which shows a deep cone-shaped depression at the surface facing the intermembrane space. At its base was found the signature sequence of these nucleotide carriers (R R R M M M). The cavity has a maximal diameter of 20 Å and a depth of 30 Å. The fold of the three repeat elements is very similar. Each odd-numbered helix exhibits a sharp kink, due to a conserved prolyl residue located in the conserved P X(D/E) X X (K/R) motif, characteristic of all mitochondrial carriers. The even-numbered helices pass straight through the membrane without a kink. The structure reveals large hydrophilic surfaces in the interior of the conical pit, due to the weak hydrophobicities of these proteins. A positive electrostatic surface potential on the matrix side and at the bottom of the pit provides the force for anionic substrate binding. Two lipid molecules, both cardiolipin molecules, are tightly bound to the carrier.
The mitochondrial uncoupling protein 2 structure has been determined by NMR molecular fragment searching (Berardi et al., 2011). UCP2 closely resembles the bovine ADP/ATP carrier, but the relative orientations of the helical segments are different, resulting in a wider opening on the matrix side of the inner membrane. Nitroxide-labelled GDP binds inside the channel and seems to be closer to transmembrane helices 1-4 (Berardi et al., 2011). The expression patterns and functions of different UCP homologs have been reviewed (Monteiro et al. 2021). Mitochondrial uncoupling proteins UCP1 and UCP2 execute their mitochondrial uncoupling function through different molecular mechanisms. Non-shivering thermogenesis by UCP1 is mediated through a transmembrane dissipation of the proton motive force to create heat during sympathetic stimulation. UCP2, on the other hand, modulates through the interaction with methylated MICU1 (TC# 8.A.44.1.1) the permeability of the cristae junction, which acts as an isolator for the cristae-located mitochondrial membrane potential. Oflaz et al. 2023 discussed and compared the molecular mechanism of UCP1 in brown adipose tissue and UCP2 in aged and cancer non-excitable cells that contribute to mitochondrial uncoupling, and the synergistic effects of both UCPs with the mitochondrial Ca2+ uptake machinery.
The transport substrates of MC family members may bind to the bottom of the cavity, and translocation results in a transient transition from a 'pit' to a 'channel' conformation (Kunji and Robinson, 2006; Robinson and Kunji, 2006). The inhibitor, carboxyatractyloside, probably binds where ADP binds, in the pit on the outer surface, thus blocking the transport cycle. Another inhibitor, bongkrekic acid, is believed to stabilize a second conformation, with the pit facing the matrix. In this conformation, the inhibitor may bind to the ATP-binding site. Functional and structural roles for residues in the TMSs have been proposed (Cappello et al., 2006, 2007). The mitochondrial carrier signature, Px[D/E]xx[K/R], of carriers is probably involved both in the biogenesis and in the transport activity of these proteins (Zara et al., 2007). A homologue has been identified in the mimivirus genome and shown to be a transporter for dATP and dTTP (Monné et al., 2007).
One of the MC family members, the uncoupling protein, UCP1 (TC# 2.A.29.3.1), functions to dissipate the proton motive force, thereby generating heat. This protein has been shown to be capable of transporting fatty acids, long chain alkylsulfonates and chloride. It is believed to allow transport of protons down their electrochemical gradient in a cyclic, fatty acid-dependent process by first exporting fatty acyl anions and then allow the free diffusion of the protonated fatty acid across the bilayer into the mitochondrion. UNC1 is therfore probably an anion translocator that may not require that transport occurs by an antiport mechanism. The fatty acid behaves as a cycling protonophore (Garlid et al., 2000). UNC1 uses coenzyme Q (ubiquinone) as a cofactor (Echtay et al., 2000). Like many other MC family members, uncoupling proteins are found in the mitochondria of plants as well as animals. Various compounds such as the reactive aldehyde (produced under oxidative stress conditions), 4-hydroxy-2-nonenal, as well as trans-retinal and other 2-alkenals activate uncoupling via UCP1-3 (TC #2.A.29.3.1) as well as the ATP/ADP antiporter (TC #2.A.29.1.1) (Echtay et al., 2003).
Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). Upon activation by long-chain fatty acids (LCFAs), UCP1 increases the conductance of the inner mitochondrial membrane (IMM) to make BAT mitochondria generate heat rather than ATP. UCP1 transports H+. UCP1 is an LCFA anion/H+ symporter (Fedorenko et al. 2012), but the LCFA anions cannot dissociate from UCP1 due to hydrophobic interactions established by their hydrophobic tails, and UCP1 effectively operates as an H+ carrier activated by LCFA. A similar LCFA-dependent mechanism of transmembrane H+ transport may be employed by other UCP members and be responsible for mitochondrial uncoupling and regulation of metabolic efficiency in various organisms and tissues.
Mitochondrial transporters have 3 homologous repeats and a structure with pseudosymmetry. Each repeat is folded into 2 transmembrane α-helices linked by a short α-helix on the matrix side and contains the signature motif PX[DE]XX[RK]. The proline residues kink the odd-numbered transmembrane α-helices, and the charged residues form a salt-bridge network connecting the C-terminal ends of the transmembrane α-helices, closing the transporter on the matrix side. During the transport cycle, the carriers form states in which the substrate-binding state of the carrier is open to the mitochrondrial intermembrane space and matrix, respectively. According to the single binding center-gating pore mechanism, interconversion of the 2 conformational states via a transition intermediate leads to substrate translocation. In the cytoplasmic state, a central substrate-binding site has been identified by applying chemical and distance constraints to comparative models. The substrates bind to 3 major sites on the even-numbered α-helices, which are related by symmetry and located approximately in the middle of the membrane. Yeast ADP/ATP carriers function as monomers (Bamberg et al., 2007).
Residues that are important for the transport mechanism are likely to be symmetrical, whereas residues involved in substrate binding will be asymmetrical reflecting the asymmetry of the substrates. By scoring the symmetry of residues in the sequence repeats, Robinson et al. (2008) identified the substrate-binding sites and salt bridge networks that are important for transport. The symmetry analyses provides an assessment of the role of residues and provides clues to the chemical identities of substrates of uncharacterized transporters. Downy mildew (Peronospora belbahrii, Peronospora effusa, and Peronospora tabacina,
which are specialized pathogens of basil, spinach, and tobacco,
respectively)-causing plant pathogens are biotrophic oomycetes that transport essential nutrients from their hosts to grow. Gene transcripts encoding the ADP/ATP translocase and the mitochondrial
phosphate carrier protein were the most abundant mRNAs detected in each
Peronospora species (Johnson et al. 2023).
The mitochondrion is one of the defining characteristics of eukaryotic cells, and to date, no eukaryotic lineage has been shown to have lost mitochondria entirely. In certain anaerobic or microaerophilic lineages, however, the mitochondrion has become severely reduced; it lacks a genome and no longer synthesizes ATP. One example of such a reduced organelle, called the mitosome, is found in microsporidian parasites. Only a few mitosomal proteins are encoded in the complete genome of the microsporidian, Encephalitozoon cuniculi, no proteins of the mitochondrial carrier family were identified. However, the microsporidian, Antonospora locustae, has a protein that is heterologously targeted to mitochondria in Saccharomyces cerevisiae (Williams et al., 2008). The protein is phylogenetically allied to the NAD+ transporter of S. cerevisiae, but it has high specificity for ATP and ADP when expressed in E. coli. An ADP/ATP carrier may provide ATP for essential ATP-dependent mitosomal processes such as Hsp70-dependent protein import and export of iron-sulfur clusters to the cytosol.
BID, a proapoptotic BCL-2 family member, plays an essential role in the tumor necrosis factor alpha (TNF-alpha)/Fas death receptor pathway in vivo. Activation of the TNF-R1 receptor results in the cleavage of BID into truncated BID (tBID), which translocates to the mitochondria and induces the activation of BAX or BAK. In TNF-alpha-activated FL5.12 cells, tBID becomes part of a 45-kDa cross-linkable mitochondrial complex. Grinberg et al. (2005) described the biochemical purification of this complex and the identification of mitochondrial carrier homolog 2 (Mtch2; TC# 2.A.29.25.2) as part of this complex. Mtch2 is similar to members of the mitochondrial carrier family. Mtch2 is an integral outer membrane protein exposed on the surface of mitochondria. Mtch2 resides in a protein complex of ca. 185 kDa, and the addition of TNF-alpha to these cells leads to the recruitment of tBID and BAX to this complex. Thus, Mtch2 is a mitochondrial target of tBID. The Mtch2-resident complex probably participates in the mitochondrial apoptotic program (Grinberg et al., 2005; Gross, 2005).
The ADP/ATP carrier is electrogenic
(electrophoretic), the GTP/GDP carrier is dependent on the pH gradient, the aspartate/glutamate
carrier is dependent on both, and the oxoglutarate/malate carrier is independent of them (Monné and Palmieri 2014). The bovine ADP/ATP carrier consists of a six-transmembrane alpha-helix bundle with a
pseudo-threefold symmetry and a closed matrix gate. By using this structure as a template in
homology modeling, residues engaged in substrate binding and the formation of a cytoplasmic gate in
MCs have been proposed. The functional importance of the residues of the binding site, the matrix,
and the cytoplasmic gates is supported by transport activities of different MCs with single point
mutations. Cumulative evidence has been used to postulate a general transport mechanism for MCs (Monné and Palmieri 2014).
The ER delivery of endogenous mitochondrial transmembrane proteins, especially those belonging to the SLC25A mitochondrial carrier family, is dependent on the guided entry of tail-anchored proteins (GET) complex. Without a functional GET pathway, non-imported mitochondrial proteins destined for the ER are alternatively sequestered into Hsp42-dependent protein foci. Loss of the GET pathway is detrimental to yeast cells experiencing mitochondrial import failure and prevents re-import of mitochondrial proteins from the ER via the ER-SURF pathway (Xiao et al. 2021).
Mitochondrial heat production is crucial for the maintenance of body
temperature, regulation of the pace of metabolism, and prevention of
oxidative damage. Mitochondria produce heat as
the result of H+ leak across their inner membrane. Bertholet and Kirichok 2022 provided an assessment of the current field of mitochondrial H+ leak and thermogenesis, with a focus on the molecular mechanisms
involved and regulation of uncoupling protein 1 and the
ADP/ATP carrier, the two proteins that mediate mitochondrial H+ leak.
The generalized transport reaction for carriers of the MC family is:
S1 (out) + S2 (in) ⇌ S1 (in) + S2 (out)
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This family belongs to the Mitochondrial Carrier (MC) Superfamily.
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Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.1.1 | Mitochondrial ATP/ADP antiporter 2 (SLC25A5; ANT2) of 298 aas and 6 TMSs; it facilitates exchange of ADP and ATP between the cytosol and mitochondrial matrix (inhibited by carboxyatractyloside and bongkrekate) (Clémençon et al. 2013). Modification of lysyl residues with fluorescamine induces Ca2+ permeability (Buelna-Chontal et al. 2014). Ca2+ induces oxidative stress, which increases lipid peroxidation and ROS generation, collapses the transmembrane potential and releases cytochrome c (Correa et al. 2018). Thus, pore opening in the inner mitochondrial membrane results from the binding of Ca2+ to the adenine nucleotide translocase. It is methylated by
FAM173A, a mitochondrial lysine-specific methyltransferase that targets ANTs 2 and 3, and affects mitochondrial
respiration (Małecki et al. 2019). | Animals | SLC25A5 of Homo sapiens |
|
2.A.29.1.10 | Solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6. It is an ADP/ATP exchanger (Clémençon et al. 2013). | Animals | SLC25A6 of Homo sapiens |
|
2.A.29.1.2 | Mitochondrial ADP/ATP carrier 1 (AAC1); ADP/ATP translocase 1; adenine nucleotide translocator 1 (ANT1); adPEO, Sengers syndrome (SLC25A4). Valine 181 is critical for the nucleotide exchange activity (De Marcos Lousa et al. 2005). Mice have three ANTs, and if all three are knocked out, the mitochondrial permeability transition pore (MPTP) can not form, although with only two eliminated, it still can, suggesting the an ANT is an essential constituent of the MPTP (Karch et al. 2019). The MPT provides a mechanism of skeletal muscle atrophy that operates through mROS emission and caspase-3 activation (Burke et al. 2021). Inhibition of carnitine palmitoyltransferase 1A aggravates fatty liver graft injury by promoting the mitochondrial permeability transition (Xue et al. 2021). Upon protein kinase C (PKC) inactivation, the cytoprotective compound, bisindolylpyrrole, can induce prolonged transient MPTP, causing apoptosis in a cyclophilin D (CypD)-dependent manner through the VDAC1/2-regulated ANT-associated pore (Koushi et al. 2020). ANT1 mediates H+ transport, but only in the presence of long-chain fatty acids (FA), as already known for UCPs. It depends on FA chain length and saturation, implying that FA transport is confined to the lipid-protein interface. Purine nucleotides with the preference for ATP and ADP inhibited H+ transport, as do inhibitors of ATP/ADP transport, carboxyatractyloside and bongkrekic acid (Kreiter et al. 2021). Constraints imposed by ANT and cyclophilin D, putative components or regulators of the MPT pore, are associated with the enhanced resistance to Ca2+-induced MPT (Sartori et al. 2022). | Animals | SLC25A4 of Homo sapiens |
|
2.A.29.1.3 | Adenine nucleotide transporter, ANT, or ATP:ADP carrier AAC1 (one of three paralogues). Transports heme and heme precursor protoporphyrin IX (PP IX) as well as ATP and ADP (Azuma et al. 2008). | Fungi | AAC1 of Saccharomyces cerevisiae (P04710) |
|
2.A.29.1.4 | The Hydrogenosome ADP/ATP carrier (Van der Giezen et al., 2002) | Fungi | Hydrogenosome ADP/ATP carrier of Neocallimastix frontalis (AAK 71468) |
|
2.A.29.1.5 | ADP (Km = 40 µM)/ATP (Km = 100 µM) antiporter, ACC1 (three isoforms, AAC1, 2 and 3 were characterized where AAC3 has higher affinities (10-22 µM) (Haferkamp et al., 2002). | Plants | ACC1 of Arabidopsis thaliana
(P31167) |
|
2.A.29.1.6 | The Endoplasmic Reticular Adenine Nucleotide Transporter, ER-ANT1 (probable ATP:ADP exchanger; Leroch et al., 2008) | Plants | ER-ANT1 of Arabidopsis thaliana (Q0WQJ0) |
|
2.A.29.1.7 | ADP:ATP carrier 2, Aac2 (Lethal with loss of Sal1, (2.A.29.23.2) but independent of its AAC activity (Kucejova et al., 2008)). The x-ray structure suggests a novel domain-based alternating-access transport mechanism (Ruprecht et al. 2014). | Yeast | Aac2 of Saccharomyces cerevisiae (P18239) |
|
2.A.29.1.8 | Mitochondrial ADP/ATP carrier-4, ANT4, of 315 aas and 6 TMSs. It may serve to mediate energy generating and energy
consuming processes in the distal flagellum, possibly as a nucleotide
shuttle between flagellar glycolysis, protein phosphorylation and
mechanisms of motility (Kim et al. 2007). | Animals | SLC25A31 of Homo sapiens |
|
2.A.29.1.9 | ADP/ATP carrier #3, AAC3 (90% identical to 2.A.29.1.7) (#2)). Prolines in TMSs 1,3, and 5 are important for function (Babot et al., 2012). The x-ray structure suggests a novel domain-based alternating-access transport mechanism (Ruprecht et al. 2014). Although the transporter catalyzes the translocation of substrate, the
substrate also facilitates interconversion between alternating states (Brüschweiler et al. 2015). | Yeast | ADP/ATP exchanger-3 (ACC3) of Saccharomyces cerevisiae (P18238) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.10.1 | Flavin adenine dinucleotide (FAD) carrier (FADC; FLX1) (catalyzes FAD export from the mitochondrion) (Bafunno et al., 2004) | Yeast | FLX1 of Saccharomyces cerevisiae |
|
2.A.29.10.10 |
Mitochondrial NAD /NADP carrier, NDT2; counter exchange substrates include ADP and AMP (Palmieri et al., 2009). | Plants | NDT2 of Arabidopsis thaliana (Q8RWA5) |
|
2.A.29.10.11 |
Chloroplastic (plastidic) NAD/NADP carrier, NDT1; of 312 aas and 6 or 7 TMSs. It catalyzes counter exchange (antiport) of substrates: ADP and AMP (Palmieri et al., 2009). | Plants | NDT1 of Arabidopsis thaliana (O22261) |
|
2.A.29.10.12 | Mitochondrial carrier, AMC1; MC2, (unknown substate) of 360 aas and 6 or 7 TMSs. | | AMC1 of Plasmodium falciparum |
|
2.A.29.10.2 | Mitochondrial folate transporter, hMFT | Animals | SLC25A32 of Homo sapiens |
|
2.A.29.10.3 |
Chloroplast folate/folate derivative transporter, AtFOLT1 (Bedhomme et al., 2005; Haferkamp and Schmitz-Esser 2012) | Plants | AtFOLT1 of Arabidopsis thaliana (CAH65737) |
|
2.A.29.10.4 | Mitochondrial pyrimidine nucleotide transporter, RIM2 (transports TTP (Km= 200 μM), UTP (Km= 400 μM) and CTP (Km= 440 μM). Catalyzes electroneutral TTP/TMP and TTP/TDP antiport. Deoxy pyrimidine nucleotides are also transported) (Marobbio et al., 2006). Pyrimidine trinucleotide transporter, RIM2 (transports TTP, CTP and UTP) (Todisco et al., 2006) | Yeast | RIM2 of Saccharomyces cerevisiae
(P38127) |
|
2.A.29.10.5 | The mitochondrial NAD+ uptake transporter, Ndt1 (also transports (d)AMP and (d)GMP but not α-NAD+, NADH, NADP+, or NADPH. Transport is saturable with an apparent Km of 0.38mM for NAD+). (70% identical to Ndt2 which also takes up NAD+). The main role of Ndt1p and Ndt2p is to import NAD+ into mitochondria by unidirectional transport or by exchange with intramitochondrially generated (d)AMP and (d)GMP (Todisco et al., 2006) | Yeast | Ndt1 of Saccharomyces cerevisiae (P40556) |
|
2.A.29.10.6 | solute carrier family 25 (pyrimidine nucleotide carrier ), member 36 | Animals | SLC25A36 of Homo sapiens |
|
2.A.29.10.7 | solute carrier family 25 (pyrimidine nucleotide carrier), member 33 | Animals | SLC25A33 of Homo sapiens |
|
2.A.29.10.8 | Mitochondrial nicotinamide adenine dinucleotide transporter 2, NDT2 (Mitochondrial NAD+ transporter 2) (Todisco et al. 2006). | Fungi | YEA6 of Saccharomyces cerevisiae |
|
2.A.29.10.9 | ADP/ATP-specific mitochondrial carrier (MC) in mitosomes (reduced mitochondria incapable of ATP synthesis) (Williams et al., 2008). | Microsporidian | MC in Antonospora locustae (Q4VFZ9) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.11.1 | The Plastid (Amyloplast) ADP-glucose transporter Brittle endosperm 1 (BT1) (Kirchberger et al., 2007). | Plants | BT1 of Zea mays |
|
2.A.29.11.2 | The Adenine nucleotide uniporter, BT1 (Leroch et al., 2005). | Plants | BT1 of Solanum tuberosum (Q9ZNY4) |
|
2.A.29.11.3 | The plastid ADP-glucose transporter, Nst1 (~90% identical to and probably orthologous with 2.A.29.11.1.) (Haferkamp, 2007). | Plants | Nst1 of Hordeum vulgare (Q6E5A5) |
|
2.A.29.11.4 | Adenine nucleotide (ATP, ADP) carrier, ANT1; BRITTLE-1. Present in both mitochondria and plastids (Haferkamp and Schmitz-Esser 2012). | Plants | ANT1 of Arabidopsis thaliana |
|
2.A.29.11.5 | Hydrogenosome ATP/ADP antiporter, HMP31 (Tjaden et al., 2004) | Anaerobic flagellates | HMP31 of Trichomonas gallinae (AAP30846) |
|
2.A.29.11.6 | ADP:ATP carrier-2 of 6 TMSs and 401 aas. | | Carrier of Trichomonas vaginalis |
|
2.A.29.11.7 | Mitochondrial carrier of 304 aas and 6 TMSs. | | Carrier of Trichomonas vaginalis |
|
2.A.29.11.8 | Putative Thiamine-pyrophosphate (TPP):nucleotide antiporter, TPC or DNG, of 576 aas and 6 TMSs with 1 TMS (N-terminal) + 5 TMSs (residues 380 -576) (Wunderlich 2022). | | TPC of Plasmodium falciparum |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.12.1 | Grave’s disease carrier (GDC) protein. Transports coenzyme A and/or a coenzyme A precursor (Vozza et al. 2016). SLC25A16 is the human orthologue. | Mammals | GDC of Bos taurus |
|
2.A.29.12.2 | Mitochondrial exchange transporter for Coenzyme A and adenosine 3', 5'-diphosphate, SLC25A42 (also transports dephospho-Coenzyme A, and ADP;
Fiermonte et al. 2009). | Animals | SLC25A42 of Homo sapiens |
|
2.A.29.12.3 | solute carrier family 25; mitochondrial carrier; Graves disease autoantigen, member 16. It is a Coenzyme A transporter (Gutiérrez-Aguilar and Baines 2013). | Animals | SLC25A16 of Homo sapiens |
|
2.A.29.12.4 | Mitochondrial Coenzyme A carrier protein, LEU5 or Leu-5 (Gutiérrez-Aguilar and Baines 2013). | Fungi | LEU5 of Saccharomyces cerevisiae |
|
2.A.29.12.5 | Coenzyme A transporter of 331 aas (Zallot et al. 2013). | Plants | Coenzyme A transporter of Arabidopsis thaliana |
|
2.A.29.12.6 | Coenzyme A transporter of 325 aas (Zallot et al. 2013).
| Plants | Coenzyme A transporter of Arabidopsis thaliana |
|
2.A.29.12.7 | Dephospho-coenzyme A (dPCoA) carrier, dPCoAC, of 365 aas and 6 TMSs. dPCoA is the best substrate, but ADP and dADP are also transported. Coenzyme A is not transported but is a strong competive inhibitor (Vozza et al. 2016). Formerly called "alternative testis transcripts open reading frame A". | | dPCoAC of Drosophila melanogaster (Fruit fly) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.13.1 | Succinate/fumarate antiporter, Sfc1, of 322 aas; essential for growth on ehtanol and acetate (Palmieri et al. 1997; Palmieri et al. 2006). | Yeast | ACR1 of Saccharomyces cerevisiae |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.14.1 | Mitochondrial Ca2+-activated aspartate/glutamate antiporter carrier with Ca2+-binding EF-hand domain, Aralar | Animals | SLC25A12 of Homo sapiens |
|
2.A.29.14.10 | Calcium-binding mitochondrial carrier protein Aralar1 of 690 aas. | | Aralar1 of Verticillium alfalfae (Verticillium wilt of alfalfa) (Verticillium albo-atrum) |
|
2.A.29.14.11 | Uncharacterized protein of 1149 aas with 7 N-terminal TMSs; only the N-terminal 360 aas are homologous to other members of the MC family. | | UP of Aphanomyces invadans |
|
2.A.29.14.2 | Mitochondrial Ca2+-activated aspartate/glutamate antiporter carrier with Ca2+-binding EF-hand domain, Citrin (defects in humans cause type II citrullinemia) | Animals | SLC25A13 of Homo sapiens |
|
2.A.29.14.3 | Mitochondrial glutamate carrier 1 (GC1); glutamate:H+ symporter 1 (SLC25A22). It plays a role in glucose-stimulated insulin secretion by β-cells (Casimir et al., 2009), and is responsible for migrating partial seizures in neonatal infancy (MPSI), a severe condition with few known
etiologies (Poduri et al. 2013). Early infantile epileptic encephalopathy (EIEE) is a heterogeneous group of severe forms of age-related developmental and epileptic encephalopathies with onset during the first weeks or months of life. EIEE type 3 is caused by variants affecting the function of SLC25A22, which is also responsible for epilepsy of infancy with migrating focal seizures (EIMFS). Lemattre et al. 2019 reported a family with a less severe phenotype of EIEE type 3. Functional studies showed that glutamate oxidation was defective. There are three groups according to the severity of the SLC25A22-related disorders. The variants were classified according to the location of the mutation, depending on the protein domain; patients with two variants located in helical transmembrane domains presented a severe phenotype, whereas patients with at least one variant outside helical transmembrane domains presented a milder phenotype. Thus, there seems to be a continuum of disorders related to SLC25A22 (Lemattre et al. 2019). | Animals | SLC25A22 of Homo sapiens |
|
2.A.29.14.4 | Yeast mitochondrial aspartate/glutamate antiporter, Agc1 (Cavero et al., 2003) (also catalyzes glutamate uniport and glutamate:proton symport (Palmieri et al. 2006). Comprised of 902 aas; has a 500 residue N-terminal hydrophilic domain as well as a C-terminal 100 residue hydrophilic domain. Both domains are uniquely found in members of the 2.A.29.14 subfamily. | Yeast | Agc1 of Saccharomyces cerevisiae (NP_015346) |
|
2.A.29.14.5 | solute carrier family 25 (glutamate carrier), member 18 | Animals | SLC25A18 of Homo sapiens |
|
2.A.29.14.6 | Solute carrier family 25, member 40, SLC25A40 of 338 aas and 6 TMSs. This mitochondrial inner membrane transporter can be mutated (Y125C) to give hypertriglyceridemia (Rosenthal et al. 2013). It may also be involved in primary Sjögren's syndrome (pSS), a prevalent and disabling form of fatigue (Norheim et al. 2014). SLC25A40 facilitates anticancer drug resistance in human leukemia K562 cells (Kudo et al. 2023). | Animals | SLC25A40 of Homo sapiens |
|
2.A.29.14.7 | solute carrier family 25, member 44, SLC25A44 of 314 aas and 6 TMSs in a 3 + 3 arrangement. The GBA-370Rec Parkinson's disease risk haplotype harbors a potentially pathogenic variant in the SLC25A44 mitochondrial gene (Goldstein et al. 2021). | Animals | SLC25A44 of Homo sapiens |
|
2.A.29.14.8 | Solute carrier family 25 member 39 | Animals | SLC25A39 of Homo sapiens |
|
2.A.29.14.9 | MC family homologue of 327 aas and 6 TMSs | Plants | MCP homologue of Ostreococcus lucimarinus |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.15.1 | Oxaloacetate/malonate/sulfate/thiosulfate transporter, OAC1 | Yeast | Oxaloacetate carrier (OAC1) of Saccharomyces cerevisiae |
|
2.A.29.15.2 | solute carrier family 25, member 35 | Animals | SLC25A35 of Homo sapiens |
|
2.A.29.15.3 | solute carrier family 25, member 34 | Animals | SLC25A34 of Homo sapiens |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.16.1 | Reported to be a deoxynucleotide (enzyme), the deoxynucleotide carrier (DNT) (all four dNDPs and less efficiently, all four dNTPs are transported, but not dNMPs, NMPs or nucleosides). It is also a thiamin pyrophosphate (TPP) transporter responsible for Amish lethal microencephaly brain development retardation (MCPHA) and α-ketoglutarate acidurua when defective (Arco and Satrústegui, 2005; Lindhurst et al., 2006; Iacopetta et al., 2010). | Animals | SLC25A19 of Homo sapiens |
|
2.A.29.16.2 | The thiamin pyrophosphate (TPP) transporter, Tpc1; catalyzes thiamin pyrophosphate/thiamin monophosphate excange (Palmieri et al. 2006). Also transports pyrophosphate, ADP, ATP and other nucleotides (Iacopetta et al., 2010). | Animals | Tpc1 of Drosophila melanogaster (Q7K0L7) |
|
2.A.29.16.3 | Uncharacterized mitochondrial carrier C1604.04 | Yeast | SPBC1604.04 of Schizosaccharomyces pombe |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.17.1 | Peroxisomal ATP/ADP/AMP antiporter, Ant1 (Ypr128cp) (Palmieri et al. 2006). | Yeast | Ant1 of Saccharomyces cerevisiae (AAB68270) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.18.1 | Mitochondrial S-adenosylmethionine (SAM) carrier, Sam5p or PET8 (Marobbio et al., 2003). Catalyzes the exchange of SAM for S-adenosylhomoserine as well as biotin and lipoate transport (Palmieri et al. 2006). | Yeast | Sam5p of Saccharomyces cerevisiae (P38921) |
|
2.A.29.18.2 | The plastid S-Adenosylmethionine importer, SAMT1 (regulates plastid biogenesis and plant development; catalyzes the counter-exchange of SAM with SAM and with S-adenosylhomocysteine) (Bouvier et al., 2006). Also present in the mitochondrion (Haferkamp and Schmitz-Esser 2012). | Plants | SAMT1 of Arabidopsis thaliana (Q94AG6) |
|
2.A.29.18.3 | Solute carrier family 25 (S-adenosylmethionine (SAM) carrier), member 26 of 275 aas and 6 TMSs. It is responsible for the uptake of SAM into mitochondria and when defective by mutation gives rise to combined oxidative phosphorylation deficiency 28 (COXPD28) (Ji et al. 2021).
| Animals | SLC25A26 of Homo sapiens |
|
2.A.29.18.4 | Uncharacterized protein of 369 aas and 6 TMSs | | UP of Chlamydomonas reinhardtii (Chlamydomonas smithii) |
|
2.A.29.18.5 | Inner membrane mitochondrial magnesium exporter, Mme1 of 347 aas and 6 (- 8?) TMSs. Deletion of MME1 significantly increased steady-state mitochondrial Mg2+ concentrations, while overexpression decreased them. Measurements of Mg2+ exit from proteoliposomes reconstituted with purified Mme1 provided
definite evidence that Mme1 is an Mg2+ exporter (Cui et al. 2015). | | Mme1 of Saccharomyces cerevisiae |
|
2.A.29.18.6 | Inner membrane mitochondrial magnesium exporter, Mme1 of 347 aas and 6
(- 8?) TMSs. Deletion of MME1 significantly increased steady-state
mitochondrial Mg2+ concentrations, while overexpression decreased them. Measurements of Mg2+ exit from proteoliposomes reconstituted with purified Mme1 provided
definite evidence that Mme1 is an Mg2+ exporter (Cui et al. 2015). The G-M-N motif determines ion selectivity, probably together with
the negatively charged loop at the entrance of the channel, thereby
forming the selectivity filter (Sponder et al. 2013). | | Mme1 of Saccharomyces cerevisiae |
|
2.A.29.18.7 | Putative mitochondrial carrier, MTM1 or MC3 of 380 aas and 6 or 7 TMSs. | | MTM1 of Plasmodium falciparum |
|
2.A.29.18.8 | Mitochondrial carrier protein, SamC or PET8, probably takes up S-adenosyl-methionine (SAM) and exports S-adenosyl-homocysteine (SAH) of 256 aas and 6 TMSs. | | SamC of Plasmodium falciparum |
|
2.A.29.18.9 | Mitochondrial carrier, MME1 or MC1, (substrate unknown) of 330 aas and 6 TMSs. | | MME1 of Plasmodium falciparum |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.19.1 | Mitochondrial ornithine carrier 2 (ORC2 or OrnT2) (transports ornithine, citrulline, lysine, arginine, histidine); HHH syndrome (SLC25A2). Catalyzes ornithine:citrulline antiport and ornithine:H+ antiport (Tonazzi and Indiveri, 2011). | Animals | SLC25A2 of Homo sapiens |
|
2.A.29.19.2 |
Mitochondrial ornithine transporter (ornithine/citrulline exchanger), SLC25A15 or Orc1. Catalyzes a vital step in the urea cycle, interconnecting the cytosolic and mitochondrial components for the cycle (Moraes and Reithmeier 2012). | Animals | SLC25A15 of Homo sapiens |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.2.1 | Oxoglutarate/malate antiporter. Also transports porphyrin derivatives: Fe-protoporphyrin IX, coproporphyrin III, hemin, etc. (Kabe et al., 2006). Plays roles in the malate-aspartate shuttle, the oxoglutarate-isocitrate shuttle and gluconeogenesis. Functional residues have been identified (Cappello et al. 2007). | Animals | Oxoglutarate/malate carrier of Bos taurus |
|
2.A.29.2.10 | The dicarboxylate-tricarboxylate carrier (PfDTC) catalyzes oxoglutarate-malate, oxoglutarate-oxaloacetate, or oxoglutarate-oxoglutarate exchange as well as with several di- and tri-carboxylates (Nozawa et al., 2011). | Alveolata | DTC of Plasmodium falciparum (Q8IB73) |
|
2.A.29.2.11 | solute carrier family 25 (mitochondrial carrier; oxoglutarate/malate carrier), member 11 | Animals | SLC25A11 of Homo sapiens (Q9CR62) |
|
2.A.29.2.12 | Solute carrier family 25 member 52 (Mitochondrial carrier triple repeat protein 2) | Animals | SLC25A52 of Homo sapiens |
|
2.A.29.2.13 | Mitochondrial 2-oxoglutarate/malate carrier protein (OGCP) (Solute carrier family 25 member 11) | Animals | SLC25A11 of Homo sapiens |
|
2.A.29.2.14 | Solute carrier family 25 member 51 (Mitochondrial carrier triple repeat protein 1) | Animals | SLC25A51 of Homo sapiens |
|
2.A.29.2.15 | Uncharacterized protein of 309 aas and 6 TMSs. | | UP of Reticulomyxa filosa |
|
2.A.29.2.16 | The mitochondrial dicarboxylate-tricarboxylate carrier protein (DTC) of 298 aas and 6 TMSs (Picault et al. 2002). The ortholog of Gastrodia elata has been cloned, sequenced and partially characterized (Zhao et al. 2023). | | DTC of Arabidopsis thaliana |
|
2.A.29.2.2 | Dicarboxylate (succinate/fumarate/ malate/α-ketoglutarate/ oxaloacetate) antiporter | Animals | Dicarboxylate transporter of Rattus norvegicus |
|
2.A.29.2.3 | Dicarboxylate:Pi antiporter (Pi, malate, succinate, oxaloacetate, sulfate, sulfite) | Yeast | Dicarboxylate:Pi antiporter of Saccharomyces cerevisiae |
|
2.A.29.2.4 | Mammalian oxodicarboxylate carrier (ODC; SLC25A21; 607571) (transports C5-C7 oxodicarboxylates including 2-oxoadipate and 2-oxoglutarate in an antiport reaction; also transports less well: pimelate, 2-oxopimelate, 2-amino adipate, oxaloacetate, and citrate) (Defects cause 2-oxoadipate acidemia, an inborn error of metabolism) | Animals | SLC25A21 of Homo sapiens |
|
2.A.29.2.5 | 2-oxodicarboxylate carrier 2 (ODC2) (transports the same substrates as human ODC except that 2-amino adipate is not transported while malate is) (Palmieri et al. 2006). | Yeast | ODC2 of Saccharomyces cerevisiae (Q99297) |
|
2.A.29.2.6 | Plant dicarboxylate/tricarboxylate carrier, DTC, transports dicarboxylates (such as malate, oxaloacetate, oxoglutarate, and maleate) and tricarboxylates (such as citrate, isocitrate, cis-aconitate, and trans-aconitate) | Plants | DTC of Nicotiana tabacum |
|
2.A.29.2.7 | Mitochondrial dicarboxylate carrier (DIC; SLC25A10; 606794) transports malate, succinate, phosphate, sulfate, thiosulfate | Animals | SLC25A10 of Homo sapiens |
|
2.A.29.2.8 | 2-oxodicarboxylate carrier 1 (ODC1) transports C5-C7 oxodicarboxylic acid (2-oxoadipate, 2-oxoglularate, adipate, glutarate, 2-oxopimelate, oxaloacetate, citrate and malate) (functions by a strict antiport mechanism (Palmieri et al., 2001). | Yeast | ODC1 of Saccharomyces cerevisiae (Q03028) |
|
2.A.29.2.9 | The dicarboxylate carriers, DIC1 (transports malate, oxaloacetate and succinate as well as phosphate, sulfate and thiosulfate at high rates: 2-oxoglutarate is a poor substrate (Palmieri et al., 2007)). | Plants | DIC1 of Arabidopsis thaliana (Q9SJY5) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.20.1 | Peroxisomal adenine nucleotide carrier, PMP34 (ANC; SLC25A17). Probably specific for multiple cofactors like coenzyme A (CoA),
flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and
nucleotide adenosine monophosphate (AMP), and to a lesser extend for
nicotinamide adenine dinucleotide (NAD+), adenosine diphosphate (ADP) and adenosine 3',5'-diphosphate (PAP). May catalyze the transport of free CoA, FAD and NAD+ from the cytosol into the peroxisomal matrix by a counter-exchange
mechanism. Inhibited by pyridoxal 5'-phosphate and bathophenanthroline
in vitro (Visser et al. 2002; Agrimi et al. 2012). | Animals | SLC25A17 of Homo sapiens |
|
2.A.29.20.2 | Peroxisomal adenine nucleotide carrier 2, PNC2. Transports ATP, ADP and NAD+ (Linka and Esser 2012). | Plants
| PNC2 of Arabidopsis thaliana |
|
2.A.29.20.3 | Peroxisomal nucleotide (ATP, ADP, AMP) carrier-1, PNC1 (Haferkamp and Schmitz-Esser 2012). | Plants | PNC1 of Arabidopsis thaliana |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.21.1 | Mitochondrial GTP/GDP exchange carrier (Ggc1) [also transports deoxyGTP and deoxyGDP as well as ITP and IDP but less well than GTP and GDP] [KM(GTP)=1 μM; KM(GDP)=5 μM]. Inhibited by pyridoxal-5-P, bathophenanthroline and tannic acid but not by inhibitors of the ATP-ADP carrier (Vozza et al., 2004). GGC appears to be intrinsically plastic with structural plasticity asymmetrically distributed among the three
homologous domains (Sounier et al. 2015). Chaparone proteins TIM8.13 and TIM9.10 bind to Ggc1 to facilitate membrane insertion (Sučec et al. 2020). | Yeast | Ggc1 of Saccharomyces cerevisiae (NP_010083) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.22.2 | The Mitosome (crypton) ADP/ATP carrier (Chan et al., 2005) | amoeba | Mitosome ADP/ATP carrier of Entamoeba histolytica (AAK69775) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.23.1 | Mitochondrial ATP-Mg2+/inorganic phosphate antiporter [3 isoforms in humans with 3 EF-hand CA2+ binding motifs in their N-terminal domain: Q6KCM7, Q9BV35, and Q6NUK1] (Fiermonte et al., 2004) | Animals | SLC25A25 of Homo sapiens |
|
2.A.29.23.10 | Hydrogenosome carrier of 262 aas and 6 TMSs. Referred to as AAC3 (Rada et al. 2011). | | Carrier of Trichomonas vaginalis |
|
2.A.29.23.11 | Mitochondrial carrier, AMC3 or MC6, ATP/ADP antiporter, of 590 aas and 6 TMSs in a 2 + 2 + 2 TMS arrangement. | | AMC3 of Plasmodium falciparum |
|
2.A.29.23.12 | Mitochondrial carrier, AMC2 or MC4, of 540 aas and 6 or 7 TMSs in a 2 + 2 + 2 or 3 TMS arrangement. | | AMC2 of Plasmodium falciparum |
|
2.A.29.23.2 | Mg2+-ATP/Pi carrier, Sal1 (Ca2+ binding carrier, CMC1; supressor of AAC2 lethality (EF hand Ca2+ binding motif at N-terminus). ADP:ATP carrier 2 (Kucejova et al., 2008; Traba et al., 2008) | Yeast | Sal1 of Saccharomyces cerevisiae (P48233) |
|
2.A.29.23.3 | Chloroplast thylakoid ATP/ADP antiporter, TAAC (Thuswaldner et al., 2007; Haferkamp et al., 2011). Also transports 3'-phosphoadenosine 5'-phosphosulfate (PAPS), made in the mitochondria and exported to the cytoplasm where it is involved in several aspects
of sulfur metabolism, including the biosynthesis of thiols,
glucosinolates, and phytosulfokines, and therefore also named PAPST1 (Gigolashvili et al. 2012). Expression of the PAPST1 gene is regulated by the same MYB transcription
factors that also regulate the biosynthesis of sulfated secondary
metabolites, glucosinolates. | Plants | TAAC of Arabidopsis thaliana (Q9M024) |
|
2.A.29.23.4 | The mitochondrial adenine nucleotide transporter, ADNT1 (At4g01100) (prefers AMP and ADP to ATP; not inhibited by bongkrekate or carboxyatractyloside; loss yields reduced root growth and respiration) (Palmieri et al., 2008b).
| Plants | ADNT1 of Arabidopsis thaliana (O04619) |
|
2.A.29.23.5 | Solute carrier family 25 (mitochondrial carrier; ATP-M2+/phosphate carrier), member 23 of 468 aas and 6 TMSs, SLC25A23, APC2, MCSC2, SCaMC-3. Variants are generated by alternative splicing (Del Arco 2005; Bassi et al. 2005). Glucagon regulation of oxidative phosphorylatioin requires an increase in matrix adenine nucleotides involving SCaMC-3 (Amigo et al. 2013). SLC25A23 augments mitochondrial Ca2+ uptake, interacts with MCU, and induces oxidative stress-mediated cell death (Hoffman et al. 2014). It also counteracts the PARP-1-dependent fall in mitochondrial ATP caused by excitotoxic insults in neurons (Rueda et al. 2015). CaMCs play a role in glutamate excitotoxicity and Ca2+ regulation of respiration (Rueda et al. 2016). | Animals | SLC25A23 of Homo sapiens |
|
2.A.29.23.6 | solute carrier family 25, member 41 | Animals | SLC25A41 of Homo sapiens |
|
2.A.29.23.7 | solute carrier family 25, member 43. May play a role in Paget's bone disease (Gutiérrez-Aguilar and Baines 2013). Also regulates cell cycle progression and proliferation through a putative mitochondrial checkpoint (Gabrielson et al. 2015). | Animals | SLC25A43 of Homo sapiens |
|
2.A.29.23.8 | Calcium-binding mitochondrial carrier protein SCaMC-1 (Mitochondrial ATP-Mg/Pi carrier protein 1; Mitochondrial Ca2+-dependent solute carrier protein 1; Small calcium-binding mitochondrial carrier protein 1; Solute carrier family 25 member 24). The crystal structure of the N-terminal Ca2+-binding domain has been determined and shown to undergo a large conformational change when Ca2+ binds (Yang et al. 2014). | Animals | SLC25A24 of Homo sapiens |
|
2.A.29.23.9 | Mitochondrial transporter for 3′-phospho-adenosine 5′-phosphosulfate and adenosine 5′-phosphosulfate (APS), YPR011c. Sulfate and phosphate are also transported using an antiport mechanism (Todisco et al. 2014). Inhibited by bongkrekic acid. Deletion mutants are thermal sensitive and have less methionine and glutathione. The gene is induced by thermal stress conditions (Todisco et al. 2014). | Fungi | YPR011c of Saccharomyces cerevisiae
|
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.24.1 | Brain mitochondrial carrier protein 1, BMCP1 (participates in mitochondrial proton leak) (also called uncoupling protein-5 (UCP5)) (Sanchis et al., 1998). Transports protons and chloride ions; activated by fatty acids and inhibited by purine nucleotides similarly to UCP1-3 (Hoang et al. 2012); H+ transport may be activated while Cl- transport may be inhibited by faty acids (Hoang et al. 2015). Unc5 also transports sulfur anions (sulfate, sulfite, thiosulfate), inorganic phosphate, dicarboxylates (malonate, malate, citamalate, aspartate, gultamate) and tricarboxylates (Gorgoglione et al. 2019). It catalyzes fast anion:anion exchange and slow uniport. Sulfate and thiosulfate are the most high affinity substrates (Gorgoglione et al. 2019). | Animals | SLC25A14 of Homo sapiens |
|
2.A.29.24.2 | Kidney mitochondrial carrier protein, KMCP1 (Haguenauer et al., 2005). The expression patterns and functions of different UCP homologs have been reviewed (Monteiro et al. 2021). | Animals | KMCP1 of Mus musculus (NP_080508) |
|
2.A.29.24.3 |
solute carrier family 25, member 27; UCP4. Transports protons and chloride ions; activated by fatty acids and inhibited by purine nucleotides similarly to UCP1-3 (Hoang et al. 2012). H+ transport may be activated while Cl- transport may be inhibited by fatty acids (Hoang et al. 2015). MFN2 deficiency affects calcium homeostasis in lung adenocarcinoma cells via downregulation of UCP4 (Zhang et al. 2023). | Animals | SLC25A27 of Homo sapiens |
|
2.A.29.24.4 |
solute carrier family 25, member 30; Kidney MCP1, KMCP1 or UCP6 (uncoupling protein 6). It also transports sulfur anions (sulfate, sulfite, thiosulfate),
inorganic phosphate and dicarboxylates (malonate, malate, citamalate,
aspartate) (Gorgoglione et al. 2019). It catalyzes fast anion:anion exchange and slow uniport. Sulfate and thiosulfate are the most high affinity substrates (Gorgoglione et al. 2019). | Animals | SLC25A30 of Homo sapiens |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.25.1 | The mitochondrial presenilin-associated protein (PSAP; MTCH1) binds to the PDZ domain (a QFYI motif) C-terminus of presenilin. It contains 2 solcar repeats and is 389 aas long. It is most similar to 2.A.29.23.1 and 2.A.29.12.1. There are 2 human isoforms, mitochondrial carrier homologues, MTCH1 and MTCH2, possibly involved in apoptosis (Xu et al., 1999, 2002). Its transport function is unknown (Xu et al., 1999, 2002). Surprisingly, this protein has been reported to be targetted to the outer mitochonrdial membrane (Gutiérrez-Aguilar and Baines 2013). Two proapoptotic PSAP isoforms generated by alternative splicing differ in the length of a hydrophilic loop located between two predicted transmembrane domains. Both isoforms are expressed in human and
rat tissues. PSAP probably contains multiple
mitochondrial targeting motifs dispersed along the protein (Lamarca et al. 2007). | Animals | MTCH1 of Homo sapiens (Q9NZJ7) |
|
2.A.29.25.2 | The mitochondrial carrier homologue-2 (MTCH2). Binds the BH3-interacting domain death agonist, BID. Regulated (induced) by the hepatocyte growth factor receptor, HGF/SF or Met. It has been proposed that its transport function has been lost (Robinson et al., 2012). Surprisingly, this protein has been reported to be targetted to the outer mitochondrial membrane (Gutiérrez-Aguilar and Baines, 2013). MTCH2 is a mitochondrial outer membrane protein insertase (Guna et al. 2022). They are required for insertion of biophysically diverse tail-anchored (TA), signal-anchored, and multipass proteins, but not outer membrane beta-barrel proteins. | Animals | MTCH2 of Homo sapiens (Q9Y6C9) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.26.1 | Viral mitochondrial carrier-like protein, L276 (VMC) for dATP and dTTP (237 aas) (Monné et al., 2007). | Animal virus | VMC of Mimiviridae mimivirus (Q5UPV8) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.27.1 | The ATP exchanger/symporter, LcnP (secreted via the bacterial Dot/Icm type IV secretion system into macrophages, and assembled in the mitochondrial inner membrane (Dolezal et al., 2012)). | Bacteria | LcnP of Legionella pneumophila (Q5WSP6) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.28.1 | The thiamin pyrophosphate (TPP) carrier, TPC1 (Marobbio et al., 2002). | Yeast | TPC1 of Saccharomyces cerevisiae (NP_011610) |
|
2.A.29.28.2 | Uncharacterized protein of 326 as and 6 TMSs. | | UP of Kazachstania naganishii |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.29.1 | The citrate/oxoglutarate carrier, Yhm2 (Castegna et al., 2010; Mayor et al., 1997). Ymh2 also transports oxaloacetate, succinate, and fumarate, but not malate or isocitrate. It may function in antioxidation (Castegna et al., 2010). | Yeast | Yhm2 of Saccharomyces cerevisiae (Q04013) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.3.1 | Uncoupling protein (H+; halide anions; protonated or anionic fatty acids) | Animals | Uncoupling carrier of Bos taurus |
|
2.A.29.3.2 |
Mitochondrial brown fat uncoupling protein 1 (UCP1 or UCP-1) is also called thermogenin and obesity protein (SLC25A7). It mediates adaptive thermogenesis (Azzu and Brand, 2009). It transports protons and chloride ions and is activated by fatty acids while being inhibited by purine nucleotides (Hoang et al. 2012). It functions as a long-chain fatty acid (LCFA) anion/H+ symporter, but the LCFA anion can not dissociate due to hydrophobic interactions, so it is, in effect, an H+ carrier (Fedorenko et al. 2012). Thermogenic Brown adipose tissue cells with increased UCP1 activity also have increased ATP sythase activity to allow maintenance of normal ATP levels (Guillen et al. 2013). Zhao et al. 2017 showed that fatty acids (FA) can directly bind UCP1 at a helix-helix interface site composed of residues from TMSs H1 and H6. The FA acyl chain appears to fit into the groove between H1 and H6 while the FA carboxylate group interacts with the basic residues near the matrix side of UCP1 (Zhao et al. 2017). UCP1 mediates liver injury in mice and humans by modulating mitochondrial ATP production and cell apoptosis via the ERK signaling pathway (Liu et al. 2017). Activation is achieved by retinoids of UCP1 (Tomás et al. 2004). Expression of its structural gene is influenced by emodin (Cheng et al. 2021). Repeated oral administration of flavan-3-ols induces browning in mice adipose tissues through sympathetic nerve activation, and this involves increased synthesis of UCP-1, CD137 (TC# 9.B.87.4.2) and TMEM26 (TC# 9.B.422.1.1) (Ishii et al. 2021). UCP1 has been described in detail as a sophisticated energy valve involving loose and tight conformations and H+ transport (Klingenberg 2017). H+ transport is electrophoretic and depends on fatty acids. By alternating opening of the gates, the fatty acid takes H+ from cytosol and release it to the matrix (Klingenberg 2017). ucp1, and ucp3, biomarkers for cardiac damage, were significantly upregulated by Tl+ in Danio rerio. (Chang et al. 2023). The cryo-EM structure of the GTP-inhibited state of UCP1, like its nonconducting state, has been solved (Jones et al. 2023). The purine nucleotide cross-links the transmembrane helices of UCP1 with an extensive interaction network, providing a structural basis for understanding the specificity and pH dependency of this regulatory mechanism. The analyses indicate that inhibitor binding prevents the conformational changes that UCP1 uses to facilitate proton leak (Jones et al. 2023). As noted above, UCP1 conducts protons through the inner mitochondrial membrane to uncouple mitochondrial respiration from ATP production, thereby converting the electrochemical gradient of protons into heat. UCP1 is activated by endogenous fatty acids and synthetic small molecules, such as 2,4-dinitrophenol (DNP), and is inhibited by purine nucleotides, such as ATP. Kang and Chen 2023 presented the structures of human UCP1 in the nucleotide-free state, the DNP-bound state and the ATP- bound state. The structures show that the central cavity of UCP1 is open to the cytosolic side. DNP binds inside the cavity, making contact with TMS2 and TM6. ATP binds in the same cavity and induces conformational changes in TMS2, together with the inward bending of TMSs 1, 4, 5 and 6 of UCP1, resulting in a more compact structure of UCP1. The binding site of ATP overlaps that of DNP, suggesting that ATP competitively blocks the functional engagement of DNP, resulting in the inhibition of the proton-conducting activity of UCP1 (Kang and Chen 2023). | Animals | UCP1 of Homo sapiens |
|
2.A.29.3.3 |
The uncoupling protein, UCP1 or PUMP1 (functions to relieve oxidative stress, and to allow efficient photosynthesis (Sweetlove et al., 2006). In some plants, it is activated in response to cold stress and may control reactive oxygen species (Valente et al. 2012). In addition to protons, it transports a variety of anions including aspartate, glutamate, cysteine sulfinate, cysteate, dicarboxylates (malate, oxaloacetate, oxaloglutarate), phosphate, sulfate and thiosulfate. It functions preferentially as an anion exchanger, but more slowly as an anion uniporter. A primary function may be aspartate/glutamate antiport, thereby contributing to the export of reducing equivalents from the mitochondria in photorespiration. (Monné et al. 2018). | Plants | UCP1 of Arabidopsis thaliana (O65623) |
|
2.A.29.3.4 |
Human UCP2; implicated in a variety of physiological and pathological processes including protection from oxidative stress, negative regulation of glucose sensing systems and the adaptation of fatty acid oxidation capacity to starvation. It is not involved in thermogenesis as is UCP1 (Azzu and Brand, 2009). Leucine zipper EF hand-containing transmembrane protein 1 (LetM1; 2.A.97) and uncoupling proteins 2 and 3 (UCP2/3) contribute to two distinct mitochondrial Ca2+ uptake pathways (Waldeck-Weiermair et al., 2011). UCP2 transports protons and chloride ions, is activated by fatty acids and inhibited by purine nucleotides (Hoang et al. 2012). It reduces mitochondrial Ca2+ uptake in response to intracellular Ca2+ release in pancreatic beta cells (Alam et al. 2012). Arginine residues in TMS2 are important for chloride transport without affecting fatty acid-dependent proton transport (Hoang et al. 2015). UCP2 is impermeable to water and has a fatty acid binding site related to H+ transport (Škulj et al. 2021). A biphasic proton transport mechanism for uncoupling proteins, with a focus on UCP2, has been proposed (Ardalan et al. 2021). Klotho (TC# 8.A.49) inhibits H2O2-induced oxidative stress and apoptosis in periodontal ligament stem cells by regulating UCP2 expression (Zhu et al. 2021). TMS2 functions in the formation of a stable ion channel due to the presence of arginine residues, in particular Arg88, which is a key residue for the movement of Cl- ions. An atomic-level description of the Cl- ion transport mechanism has been provided (Naz and Moin 2022). | Animals | UCP2 of Homo sapiens |
|
2.A.29.3.5 |
Human UCP3; implicated in a variety of physiological and pathological processes
including protection from oxidative stress, negative regulation of
glucose sensing systems and the adaptation of fatty acid oxidation
capacity to starving. Not involved in thermogenesis as is UCP1 (Azzu and Brand, 2009). It also modulates the activity of the sarco/endoplasmic reticulum Ca2 -ATPase (SERCA) by decreasing mitochondrial ATP production (De Marchi et al., 2011). Leucine zipper EF hand-containing transmembrane protein 1 (LetM1; 2.A.97) and uncoupling proteins 2 and 3 (UCP2/3) contribute to two distinct mitochondrial Ca2 uptake pathways (Waldeck-Weiermair et al., 2011). Transports protons and chloride ions; activated by fatty acids and inhibited by purine nucleotides (Hoang et al. 2012). | Animals | UCP3 of Homo sapiens |
|
2.A.29.3.6 | Uncouopling protein B, UCPB, of 268 aas and 5 TMSs, with TMS 5 deleted. This protein can still function as an uncoupling protein (Ito et al. 2006). | | UCPB of Symplocarpus renifolius |
|
2.A.29.3.7 | Uncoupling protein A (UCPA) of 303 aas and 6 TMSs. Functions as an uncoupling protein, transporting protons across the mitochondrial inner membrane (Ito et al. 2006). | | UCPA of Symplocarpus renifolius (skunk cabbage)
|
|
2.A.29.3.8 | Dicarboxylate transporter, UCP2 or PUMP2 of 305 aas and 6 TMSs. It transports aspartate, glutamate, non-amino acid dicarboxylates (malate, oxaloacetate, oxaloglutarate), cysteine suflinate, cysteate, and inorganic phosphate. It is a fast antiporter and a slow uniporter (Monné et al. 2018). | | UCP2 of Arabidopsis thaliana |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.30.1 | The human mitochondrial carrier (418aas; 6 TMSs) of unknown function (SLC25A46). May play a role in atopic dermatitis (Gutiérrez-Aguilar and Baines 2013). | Animals | SLC25A46 of Homo sapiens |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.31.1 | Sequence-divergent mitochondrial carrier of 394 aas and 6 TMSs, MCP14. The T. brucei MCP14 appears to be involved in energy metabolism but it also mediates drug action and is required for cell growth and viability (de Macêdo et al. 2015). TbMCP14 belongs to a trypanosomatid-specific clade of the mitochondrial carrier family. | Euglenozoa | MCP14 of Trypanosoma cruzi |
|
2.A.29.31.2 | MCP14 orthologue of 447 aas and 6 TMSs | Euglenozoa | MCP14 of Leishmania major |
|
2.A.29.31.3 | MCP14 paralogue of 361 aas and 6 TMSs | Euglenozoa | MCP14 of Trypanosoma cruzi |
|
2.A.29.31.4 | MCP14 homologue of 338 aas and 6 TMSs. | Euglenozoa | MCP14 homologue of Strigomonas culicis |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.32.1 | Putative mitochondrial 2-oxodicarboxylate carrier 2 of 296 aas and 6 TMSs. | | MC family member of Symbiodinium microadriaticum
|
|
2.A.29.32.2 | Uncharacterized protein of 330 aas and 6 TMSs. | | UP of Reticulomyxa filosa |
|
2.A.29.32.3 | The Entamoeba transmembrane mitosomal protein of 30 kDa (ETMP30) of 260 aas and 5 equally distantly spaced TMSs. Its loss results in a defect in growth and partial elongation of mitosomes (Santos et al. 2019). The aerobic mitochondrion had undergone evolutionary diversification, most notable among lineages of anaerobic protists. Entamoeba is one of the genera of parasitic protozoans that lack canonical
mitochondria, and instead possess mitochondrion-related organelles
(MROs), specifically, mitosomes. Entamoeba mitosomes exhibit
functional reduction and divergence, most exemplified by the organelle's
inability to produce ATP and synthesize iron-sulfur clusters. Instead,
this organelle is capable of sulfate activation, which has been linked
to amoebic stage conversion (Santos et al. 2019). Colocalization of hemagglutinin (HA)-tagged ETMP30 with the mitosomal
marker, adenosine-5'-phosphosulfate kinase. Mitosomal membrane
localization was indicated by immunoelectron microscopy analysis.
Transcriptional gene silencing successfully repressed RNA expression by
60%, and led to a defect in growth and partial elongation of mitosomes.
Immunoprecipitation of ETMP30 from ETMP30-HA-expressing transformant
using anti-HA antibody pulled down one interacting protein of 126 kDa.
Protein sequencing by mass spectrometry revealed this protein as a
cation-transporting P-type ATPase, previously reported to localize to
vacuolar compartments/Golgi-like structures, hinting at a possible
mitosome-vacuole/Golgi contact site (Santos et al. 2019). | | ETMP30 of Entamoeba histolytica |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.4.1 | Phosphate carrier | Animals, yeast | Phosphate carrier of Bos taurus |
|
2.A.29.4.2 | Phosphate carrier protein (PiC); mitochondrial precursor (PTP) (SLC25A3). Variants lead to a failure of inorganic phosphate
(Pi) transport across the mitochondrial membrane, loss of oxidative phosphorylation, and phenotypically varied cases of skeletal myopathy and cardiomyopathy (Bhoj et al. 2015; Calvello et al. 2018). | Animals | SLC25A3 of Homo sapiens |
|
2.A.29.4.3 | Phosphate carrier, Pic1: (PTP1; Mir1) (Hamel et al., 2004). Also transports short chain (methane) phosphonates and medium chain (C12, C14 and C16) fatty acids which competitively inhibit phosphate transport (Engstová et al. 2001). | Yeast | Pic1 of Saccharomyces cerevisiae (P23641) |
|
2.A.29.4.4 | Phosphate carrier, Pic2: (PTP2; functionally equivalent paralogue of Pic1) (Hamel et al., 2004)
| Yeast | Pic2 of Saccharomyces cerevisiae (P40035) |
|
2.A.29.4.5 | solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 3 | Animals | Phosphate carrier of Mus musculus (Q8VEM8) |
|
2.A.29.4.6 | Mitochondrial phosphate carrier-1, PiC1, AT5, PHT3;1 of 375 aas and 6 TMSs (Liu et al. 2017). | Plants | PiC1 of Arabidopsis thaliana |
|
2.A.29.4.7 | Inorganic phosphate:H+ symporter, PIC, of 324 aas and 6 TMSs. | | PIC of Plasmodium falciparum |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.5.1 | MRS3 iron (Fe2+) import carrier in the inner mitochondrial membrane; essential for erythroid iron utilization) (Mühlenhoff et al., 2003). Uptake is dependent on the pH gradient (Froschauer et al. 2009).
| Yeast | MRS3 of Saccharomyces cerevisiae |
|
2.A.29.5.2 | MRS4 iron (Fe2+) import carrier in the inner mitochondrial membrane; essential for erythroid iron utilization) (Mühlenhoff et al., 2003). Uptake is dependent on the pH gradient (Froschauer et al. 2009).
| Yeast | MRS4 of Saccharomyces cerevisiae |
|
2.A.29.5.3 | Mitochondrial iron transporter, mitoferrin (Shaw et al., 2006). Essential for erythroid iron utilization (Froschauer et al. 2009). Mitochondrial iron import regulation occurs through differential turnover of mitoferrin 1 and mitoferrin 2 (Paradkar et al., 2009) | Animals | Mitoferrin of Brachydanio rerio (Q287T7) |
|
2.A.29.5.4 | solute carrier family 25 (mitochondrial iron transporter), member 28, putative iron transporter; Mitoferrin-2 | Animals | Mitoferrin-2 of Mus musculus (Q8R0Z5) |
|
2.A.29.5.5 | solute carrier family 25 (mitochondrial iron transporter), member 37, putative iron transporter, Mitoferrin-1 | Animals | Mitoferrin-1 of Mus musculus (Q920G8) |
|
2.A.29.5.6 | Solute carrier family 25, member 38, SLC25A38; probably involved in heme biosynthesis by importing glycine and/or 5-aminolevulinate into mitochondria (Gutiérrez-Aguilar and Baines 2013). SLC25A38 congenital sideroblastic anemia has been characterized with respect to their phenotypes and genotypes based on 31 individuals from 24 families (Heeney et al. 2021). | Animals | SLC25A38 of Homo sapiens |
|
2.A.29.5.7 | Mitoferrin-1 (Mitochondrial iron transporter 1) (Mitochondrial solute carrier protein) (Solute carrier family 25 member 37) | Animals | SLC25A37 of Homo sapiens |
|
2.A.29.5.8 | Mitoferrin-2 (Mitochondrial RNA-splicing protein 3/4 homologue) (MRS3/4) (hMRS3/4) (Mitochondrial iron transporter 2) (Solute carrier family 25 member 28) | Animals | SLC25A28 of Homo sapiens |
|
2.A.29.5.9 | Putative mitochondrial ferrous iron (Fe2+) importer of 1199 aas and 6 TMSs with a 1 (N-terminus) + 3 (residues 710 - 870) + 2 (C-terminus) TMSs. | | Fe3+ importer of Plasmodium falciparum |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.6.1 | Peroxisomal carrier, PMP47. May be a transporter for several enzyme cofactors (based on similarity to human PMP34 (TC# 2.A.29.20.1) | Yeast | PMP47 of Candida boidinii |
|
2.A.29.6.2 | Peroxysomal/glyoxysomal PMP38 (PXN) of 331 aas. Mediates NAD import into peroxisomes. Favors NAD (in)/AMP(out) antiport, but can also catalyze unidirectional transport that might be essential under special conditions. Transports CoA, dephospho-CoA, acetyl-CoA, adenosine 3'',5''-diphosphate (PAP), NAD , AMP, ADP and NADH, but not ATP, GTP, GDP, NADPH, NADP or FAD. Required for peroxisomeal proliferation (Mano et al. 2011; Agrimi et al. 2012; Bernhardt et al. 2012). | Plants | PMP38 of Arabidopsis thaliana |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.7.1 | Tricarboxylate carrier (exchanges a tricarboxylate (citrate, isocitrate, cis-aconitate) + H+ for another tricarboxylate + H+, a dicarboxylate (malate, succinate) or phosphoenolpyruvate). | Animals | Citrate carrier of Rattus norvegicus |
|
2.A.29.7.2 | Citrate/malate exchange carrier CIC (CTP); tricarboxylate carrier (citrate·H+/malate, PEP) (SLC25A1). Missense mutations in the SLC25A1 gene lead to an autosomal recessive neurometabolic
disorder characterised by neonatal-onset encephalopathy with severe
muscular weakness, intractable seizures, respiratory distress, and lack
of psychomotor development, often resulting in early death. Majd et al. 2018 measured the effect of all twelve known pathogenic mutations on transport activity. These mutations abolished
transport of citrate completely, or reduced the
transport rate by >70%, indicating that impaired citrate transport is
the most likely primary cause of the disease. The human citrate carrier
predominantly transports citrate, isocitrate, cis-aconitate,
phosphoenolpyruvate and malate. Export of citrate from the mitochondrion
cannot be fully compensated by other pathways, restricting the cytosolic
production of acetyl-CoA that is required for the synthesis of lipids,
sterols, dolichols and ubiquinone, which in turn explains the severe
disease phenotypes (Majd et al. 2018). The prostate produces and
releases large amounts of citrate. Mazurek et al. 2010 cloned the citrate transporter from human prostate epithelial
cell plasma membranes.The prostatic
carrier is an isoform of the mitochondrial transporter SLC25A1 with a
different first exon. The cloned protein is the main prostatic transporter responsible
for citrate release. | Animals | SLC25A1 of Homo sapiens |
|
2.A.29.7.3 | Citrate transport protein, CTP1. Catalyzes obligatory exchange of the dibasic form of tricarboxylates (citrate and isocitrate) for other tricarboxylates. Two citrate binding sites per monomer have been identified (Ma et al., 2007). Mutations in residues in internal or external pore regions can relax the specificity, converting CTP1 into a nonspecific anion carrier. The data is consistent with outward-facing, occluded, and inward-facing states. | Yeast | CTP1 of Saccharomyces cerevisiae (P38152) |
|
2.A.29.7.4 | The fruit fly citrate uptake carrier, CIC (expressed at all stages of development; same substrate as for other eukaryotic tricarboxylate transporters (Carrisi et al., 2008).
| Animals | CIC of Drosophila melanogaster (Q7KSQ0) |
|
2.A.29.7.5 | The citrate carrier (CIC) (Madeo et al., 2009) | Animals | CIC of Anguilla anguilla (Q1ENH3) |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.8.1 | Mitochondrial carnitine/acyl carnitine carrier (CAC) | Mammals | CAC of Rattus norvegicus |
|
2.A.29.8.10 | Solute carrier family 25 member 47 (Hepatocellular carcinoma down-regulated mitochondrial carrier protein) | Animals | SLC25A47 of Homo sapiens |
|
2.A.29.8.11 | Mitochondrial glutamate carrier protein YMC2, of 329 aas and 6 TMSs. Ymc2p transports glutamate, and to a much lesser extent L-homocysteinesulfinate, but not other amino acids and tested metabolites. Transport was saturable, inhibited by mercuric
chloride and dependent on the proton gradient across the proteoliposomal
membrane. It transport glutamate across the mitochondrial inner membrane and thereby play a
role in intermediary metabolism, C1 metabolism and mitochondrial protein synthesis (Porcelli et al. 2018).
| Fungi | YMC2 of Saccharomyces cerevisiae |
|
2.A.29.8.12 | Carrier protein YMC1, mitochondrial | Fungi | YMC1 of Saccharomyces cerevisiae |
|
2.A.29.8.13 | Basic amino acid carrier2, BAC2 of 296 aas and 6 TMSs. This hyperosmotic stress-inducible porter transports proline in addition to basic amino acids (Toka et al. 2010). | Plants | BAC2 of Arabidopsis thaliana |
|
2.A.29.8.14 | Low-CO2-inducible chloroplast envelope protein, Ccp1, of 358 aas and 6 or 7 TMSs. Probabe HCO3- concentrating transporter (Atkinson et al. 2016). May be present in mitochondria rather than chloroplasts. Ccp2 (O24451) is 96% identical to Ccp1.
| | Ccp1 of Chlamydomonas reinhardtii (Chlamydomonas smithii) |
|
2.A.29.8.15 | Mitochondrial Mg2+ exporter, Mme1 of 299 aas and 6 TMSs (Cui et al. 2016). | | Mme1 of Drosophila melanogaster |
|
2.A.29.8.16 | L-glutamate transporter of 300 aas and 6 TMSs, A BOUT DE SOUFFLE or BOU. It transports glutamate across the mitochondrial inner membrane and thereby play a
role in intermediary metabolism, C1 metabolism and mitochondrial protein synthesis (Porcelli et al. 2018). It is involved in the transition from the embryonic stage to the juvenile autotrophic stage, and it required for postembryonic growth in the light.required for postembryonic growth in the light.required for postembryonic growth in the light.required for postembryonic growth in the light.is required for seedling development in the light (Lawand et al. 2002), maybe because it is essential for the function of photorespiratory metabolism (Eisenhut et al. 2013). | | BOU of Arabidopsis thaliana (Mouse-ear cress) |
|
2.A.29.8.2 | Embryonic differentiation (DIF-1) protein | Animals | DIF-1 of Caenorhabditis elegans |
|
2.A.29.8.3 | Human mitochondrial carnitine/acyl carnitine carrier, CAC; carnitine/acyl carnitine translocase (CACT). Defects in CACT (SLC25A20) cause CACT deficiency [MIM212138] (autosomal recessive; lethal) (Indiveri et al., 2011). A type of fluorescent probes (BCT) have a minimalist structural design based on the highly efficient and photostable BODIPY chromophore and carnitine as a biotargeting element. Both units are orthogonally bonded through a common boron atom, thus avoiding the use of complex polyatomic connectors. In contrast to previously known mitochondria-specific dyes, BCTs selectively label these organelles regardless of their transmembrane potential and in an enantioselective way. Carnitine-acylcarnitine translocase (CACT) is the key transporter for BCTs, which behave as acylcarnitine biomimetics (Blázquez-Moraleja et al. 2019). Long-chain fatty acylcarnitine binding to the mitochondrial carnitine/acylcarnitine carrier has been demonstrated (Zhang et al. 2022). Proline/Glycine residues of the PG-levels guide conformational changes along the transport cycle in CAC (SLC25A20). | Animals | SLC25A20 of Homo sapiens |
|
2.A.29.8.4 | Carnitine carrier, CRC1. Exchanges carnitine for acetylcarnitine (Palmieri et al. 2006). | Yeast | CRC1 of Saccharomyces cerevisiae (Q12289) |
|
2.A.29.8.5 | The carnitine:acylcarnitine exchange translocase, CACL. CACL is similar in tissue distribution to that of CACT (TC# 2.A.29.8.3); both are expressed at a higher level in tissues using fatty acids as fuels, except the brain, where only CACL is expressed (Sekoguchi et al., 2003) | Animals | CACL of Homo sapiens (Q8BL03) |
|
2.A.29.8.6 | The mitochondrial basic amino acid transporter, in mBAC1 (transports the basic L-amino acids arginine, lysine, ornithine, and histidine in order of decreasing affinity; does not transport citrulline; expressed in stems, leaves, flowers, siliques, and seedlings; Km for arg=0.2mM) (Hoyos et al., 2003) | Plants | mBAC1 of Arabidopsis thaliana (Q84UC7) |
|
2.A.29.8.7 | solute carrier family 25, member 45 of 288 aas and 6 putative TMSs. It may transport nucleobase-containing substrates (Meixner et al. 2020). | Animals | SLC25A45 of Homo sapiens |
|
2.A.29.8.8 | solute carrier family 25, member 48. May be associated with Parkinson's disease (Gutiérrez-Aguilar and Baines 2013). | Animals | SLC25A48 of Homo sapiens |
|
2.A.29.8.9 | Mitochondrial carrier protein CACL (CACT-like) (Solute carrier family 25 member 29). Transports basic amino acids (Porcelli et al. 2014). It transports arginine, lysine, homoarginine, methylarginine and, to a much
lesser extent, ornithine and histidine. Carnitine and acylcarnitines
were not transported by SLC25A29. This carrier catalyzes substantial
uniport besides counter-exchange transport and exhibits a high transport
affinity for arginine and lysine. It is saturable and inhibited by
mercurial compounds and other inhibitors of mitochondrial carriers to various degrees. The main physiological role of SLC25A29 is to import basic amino acids into mitochondria for mitochondrial protein synthesis and amino acid degradation (Porcelli et al. 2014). | Animals | SLC25A29 of Homo sapiens |
|
Examples: |
TC# | Name | Organismal Type | Example |
2.A.29.9.1 | Mitochondrial basic amino acid carrier (BAAC) | Fungi | BAAC of Neurospora crassa |
|
2.A.29.9.2 | Ornithine/arginine carrier, ORT1 or ARG11 (Palmieri et al., 1997). Catalyzes H+:ornithine antiport for the export of ornithine from mitochondria (Palmieri et al. 2006). | Yeast | ORT1 of Saccharomyces cerevisiae (Q12375) |
|
2.A.29.9.3 | Uncharacterized protein of 416 aas and 6 - 7 TMSs, MITC1. | | MITC1 of Chlamydomonas reinhardtii (Chlamydomonas smithii) |
|