1. University of Cambridge, UK

Abstract

Mitochondrial carriers are nuclear-encoded proteins, which translocate solutes across the inner mitochondrial membrane. Mitochondrial carriers are functional as monomers and have six TM alpha-helices and the termini in the mitochondrial intermembrane space.

Contents

GtoPdb is an expert-driven guide to pharmacological targets and the substances that act on them. GtoPdb is a reference work which is most usefully represented as an on-line database. As in any publication this work should be appropriately cited, and the papers it cites should also be recognized. This document provides a citation for the relevant parts of the database, and also provides a reference list for the research cited by those parts. For further details see [2].

Please note that the database version for the citations given in GtoPdb are to the most recent preceding version in which the family or its subfamilies and targets were substantially changed. The links below are to the current version. If you need to consult the cited version, rather than the most recent version, please contact the GtoPdb curators.

Database links

References

1. Agrimi G, Di Noia MA, Marobbio CM, Fiermonte G, Lasorsa FM and Palmieri F. (2004) Identification of the human mitochondrial S-adenosylmethionine transporter: bacterial expression, reconstitution, functional characterization and tissue distribution. Biochem J 379: 183-90 [PMID:14674884]
2. Buneman P, Christie G, Davies JA, Dimitrellou R, Harding SD, Pawson AJ, Sharman JL and Wu Y. (2020) Why data citation isn't working, and what to do about it Database 2020 [PMID:32367113]
3. Camacho JA, Obie C, Biery B, Goodman BK, Hu CA, Almashanu S, Steel G, Casey R, Lambert M and Mitchell GA et al.. (1999) Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter. Nat Genet 22: 151-8 [PMID:10369256]
4. De Leonardis F, Ahmed A, Vozza A, Capobianco L, Riley CL, Barile SN, Di Molfetta D, Tiziani S, DiGiovanni J and Palmieri L et al.. (2024) Human mitochondrial uncoupling protein 3 functions as a metabolite transporter. FEBS Lett 598: 338-346 [PMID:38058167]
5. Fernandez HR, Gadre SM, Tan M, Graham GT, Mosaoa R, Ongkeko MS, Kim KA, Riggins RB, Parasido E and Petrini I et al.. (2018) The mitochondrial citrate carrier, SLC25A1, drives stemness and therapy resistance in non-small cell lung cancer. Cell Death Differ 25: 1239-1258 [PMID:29651165]
6. Fiermonte G, Dolce V, David L, Santorelli FM, Dionisi-Vici C, Palmieri F and Walker JE. (2003) The mitochondrial ornithine transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. J Biol Chem 278: 32778-83 [PMID:12807890]
7. Fiermonte G, Dolce V, Palmieri L, Ventura M, Runswick MJ, Palmieri F and Walker JE. (2001) Identification of the human mitochondrial oxodicarboxylate carrier. Bacterial expression, reconstitution, functional characterization, tissue distribution, and chromosomal location. J Biol Chem 276: 8225-30 [PMID:11083877]
8. Fiermonte G, Paradies E, Todisco S, Marobbio CM and Palmieri F. (2009) A novel member of solute carrier family 25 (SLC25A42) is a transporter of coenzyme A and adenosine 3',5'-diphosphate in human mitochondria. J Biol Chem 284: 18152-9 [PMID:19429682]
9. Girardi E, Agrimi G, Goldmann U, Fiume G, Lindinger S, Sedlyarov V, Srndic I, Gürtl B, Agerer B and Kartnig F et al.. (2020) Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import. Nat Commun 11: 6145 [PMID:33262325]
10. Gorgoglione R, Porcelli V, Santoro A, Daddabbo L, Vozza A, Monné M, Di Noia MA, Palmieri L, Fiermonte G and Palmieri F. (2019) The human uncoupling proteins 5 and 6 (UCP5/SLC25A14 and UCP6/SLC25A30) transport sulfur oxyanions, phosphate and dicarboxylates. Biochim Biophys Acta Bioenerg 1860: 724-733 [PMID:31356773]
11. Huizing M, Iacobazzi V, Ijlst L, Savelkoul P, Ruitenbeek W, van den Heuvel L, Indiveri C, Smeitink J, Trijbels F and Wanders R et al.. (1997) Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient. Am J Hum Genet 61: 1239-45 [PMID:9399886]
12. Huizing M, Wendel U, Ruitenbeek W, Iacobazzi V, IJlst L, Veenhuizen P, Savelkoul P, van den Heuvel LP, Smeitink JA and Wanders RJ et al.. (1998) Carnitine-acylcarnitine carrier deficiency: identification of the molecular defect in a patient. J Inherit Metab Dis 21: 262-7 [PMID:9686371]
13. Jaiquel Baron S, King MS, Kunji ERS and Schirris TJJ. (2021) Characterization of drug-induced human mitochondrial ADP/ATP carrier inhibition. Theranostics 11: 5077-5091 [PMID:33859735]
14. Jones SA, Gogoi P, Ruprecht JJ, King MS, Lee Y, Zögg T, Pardon E, Chand D, Steimle S and Copeman DM et al.. (2023) Structural basis of purine nucleotide inhibition of human uncoupling protein 1. Sci Adv 9: eadh4251 [PMID:37256948]
15. Jones SA, Ruprecht JJ, Crichton PG and Kunji ERS. (2024) Structural mechanisms of mitochondrial uncoupling protein 1 regulation in thermogenesis. Trends Biochem Sci 49: 506-519 [PMID:38565497]
16. Jones SA, Sowton AP, Lacabanne D, King MS, Palmer SM, Zögg T, Pardon E, Steyaert J, Ruprecht JJ and Kunji ERS. (2025) Proton conductance by human uncoupling protein 1 is inhibited by purine and pyrimidine nucleotides. EMBO J 44: 2353-2365 [PMID:40021843]
17. Kang Y and Chen L. (2023) Structural basis for the binding of DNP and purine nucleotides onto UCP1. Nature 620: 226-231 [PMID:37336486]
18. Kory N, Uit de Bos J, van der Rijt S, Jankovic N, Güra M, Arp N, Pena IA, Prakash G, Chan SH and Kunchok T et al.. (2020) MCART1/SLC25A51 is required for mitochondrial NAD transport. Sci Adv 6 [PMID:33087354]
19. Kreiter J, Tyschuk T and Pohl EE. (2023) Uncoupling Protein 3 Catalyzes the Exchange of C4 Metabolites Similar to UCP2. Biomolecules 14 [PMID:38254621]
20. Lindhurst MJ, Fiermonte G, Song S, Struys E, De Leonardis F, Schwartzberg PL, Chen A, Castegna A, Verhoeven N and Mathews CK et al.. (2006) Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia. Proc Natl Acad Sci U S A 103: 15927-32 [PMID:17035501]
21. Luongo TS, Eller JM, Lu MJ, Niere M, Raith F, Perry C, Bornstein MR, Oliphint P, Wang L and McReynolds MR et al.. (2020) SLC25A51 is a mammalian mitochondrial NAD⁺ transporter. Nature 588: 174-179 [PMID:32906142]
22. Maity S and Sharma K. (2025) The mitochondrial choline transporter, SLC25A48, regulates urine and blood choline levels in humans. Kidney Int 107: 225-227 [PMID:39848743]
23. Majd H, King MS, Smith AC and Kunji ERS. (2018) Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1 lead to impaired citrate export required for lipid, dolichol, ubiquinone and sterol synthesis. Biochim Biophys Acta Bioenerg 1859: 1-7 [PMID:29031613]
24. Mayr JA, Zimmermann FA, Horváth R, Schneider HC, Schoser B, Holinski-Feder E, Czermin B, Freisinger P and Sperl W. (2011) Deficiency of the mitochondrial phosphate carrier presenting as myopathy and cardiomyopathy in a family with three affected children. Neuromuscul Disord 21: 803-8 [PMID:21763135]
25. Molinari F, Raas-Rothschild A, Rio M, Fiermonte G, Encha-Razavi F, Palmieri L, Palmieri F, Ben-Neriah Z, Kadhom N and Vekemans M et al.. (2005) Impaired mitochondrial glutamate transport in autosomal recessive neonatal myoclonic epilepsy. Am J Hum Genet 76: 334-9 [PMID:15592994]
26. Patil S, Borisov O, Scherer N, Wirth C, Schlosser P, Wuttke M, Ehret S, Hannibal L, Eckardt KU and Hunte C et al.. (2025) The membrane transporter SLC25A48 enables transport of choline into human mitochondria. Kidney Int 107: 296-301 [PMID:39084256]
27. Pena IA, Shi JS, Chang SM, Yang J, Block S, Adelmann CH, Keys HR, Ge P, Bathla S and Witham IH et al.. (2025) SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. Nat Commun 16: 978 [PMID:39856062]
28. Pyrihová E, King MS, King AC, Toleco MR, van der Giezen M and Kunji ERS. (2024) A mitochondrial carrier transports glycolytic intermediates to link cytosolic and mitochondrial glycolysis in the human gut parasite Blastocystis. Elife 13 [PMID:38780415]
29. Ruprecht JJ, Hellawell AM, Harding M, Crichton PG, McCoy AJ and Kunji ER. (2014) Structures of yeast mitochondrial ADP/ATP carriers support a domain-based alternating-access transport mechanism. Proc Natl Acad Sci U S A 111: E426-34 [PMID:24474793]
30. Ruprecht JJ, King MS, Zögg T, Aleksandrova AA, Pardon E, Crichton PG, Steyaert J and Kunji ERS. (2019) The Molecular Mechanism of Transport by the Mitochondrial ADP/ATP Carrier. Cell 176: 435-447.e15 [PMID:30611538]
31. Shi X, DeCiucis M, Grabinska KA, Kanyo J, Liu A, Lam TT and Shen H. (2024) Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis. Mol Cell 84: 802-810.e6 [PMID:38157846]
32. Shi X, Reinstadler B, Shah H, To TL, Byrne K, Summer L, Calvo SE, Goldberger O, Doench JG and Mootha VK et al.. (2022) Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. Nat Commun 13: 2483 [PMID:35513392]
33. Spaan AN, Ijlst L, van Roermund CW, Wijburg FA, Wanders RJ and Waterham HR. (2005) Identification of the human mitochondrial FAD transporter and its potential role in multiple acyl-CoA dehydrogenase deficiency. Mol Genet Metab 86: 441-7 [PMID:16165386]
34. Tavoulari S, Lacabanne D, Pereira GC, Thangaratnarajah C, King MS, He J, Chowdhury SR, Tilokani L, Palmer SM and Prudent J et al.. (2024) Distinct roles for the domains of the mitochondrial aspartate/glutamate carrier citrin in organellar localization and substrate transport. Mol Metab 90: 102047 [PMID:39419476]
35. Tavoulari S, Lacabanne D, Thangaratnarajah C and Kunji ERS. (2022) Pathogenic variants of the mitochondrial aspartate/glutamate carrier causing citrin deficiency. Trends Endocrinol Metab 33: 539-553 [PMID:35725541]
36. Titus SA and Moran RG. (2000) Retrovirally mediated complementation of the glyB phenotype. Cloning of a human gene encoding the carrier for entry of folates into mitochondria. J Biol Chem 275: 36811-7 [PMID:10978331]
37. Verkerke ARP, Shi X, Li M, Higuchi Y, Yamamuro T, Katoh D, Nishida H, Auger C, Abe I and Gerszten RE et al.. (2024) SLC25A48 controls mitochondrial choline import and metabolism. Cell Metab 36: 2156-2166.e9 [PMID:39111307]
38. Vozza A, Parisi G, De Leonardis F, Lasorsa FM, Castegna A, Amorese D, Marmo R, Calcagnile VM, Palmieri L and Ricquier D et al.. (2014) UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation. Proc Natl Acad Sci U S A 111: 960-5 [PMID:24395786]
39. Wang Y, Yen FS, Zhu XG, Timson RC, Weber R, Xing C, Liu Y, Allwein B, Luo H and Yeh HW et al.. (2021) SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. Nature 599: 136-140 [PMID:34707288]
40. Wibom R, Lasorsa FM, Töhönen V, Barbaro M, Sterky FH, Kucinski T, Naess K, Jonsson M, Pierri CL and Palmieri F et al.. (2009) AGC1 deficiency associated with global cerebral hypomyelination. N Engl J Med 361: 489-95 [PMID:19641205]
41. Zhang L, Hu W, Qiu Z, Li Z and Bian J. (2023) Opportunities and Challenges for Inhibitors Targeting Citrate Transport and Metabolism in Drug Discovery. J Med Chem 66: 9229-9250 [PMID:37428122]