Encyclopedia of Signaling Molecules

Living Edition
| Editors: Sangdun Choi

ANT

  • Grégory Tufo
  • Lorenzo Galluzzi
  • Guido Kroemer
  • Catherine Brenner
Living reference work entry
First Online:
Received:
Accepted:
DOI: https://doi.org/10.1007/978-1-4614-6438-9_175-1
How to cite

Synonyms

Adenine nucleotide translocase; ADP/ATP carrier

Historical Background

The adenine nucleotide translocase (ANT) or ADP/ATP carrier belongs to the evolutionarily conserved family of mitochondrial carriers (for a recent review, see Palmieri 2014). ANT constitutes one of the most abundant proteins of the mitochondrial inner membrane (IM), in which it is inserted via six transmembrane helices. Both the C- and N-termini of ANT face the mitochondrial matrix. ANT was first characterized as an antiporter that mediates the export of ATP from the mitochondrial matrix to the intermembrane space together with the import of ADP from the intermembrane space to the matrix (Pfaff and Klingenberg 1968) (Fig. 1a). Its antiporter activity is electrogenic, as it drives the stoichiometric exchange of ATP 4− and ADP 3−. ANT may also act as an IM channel, playing a critical role in the permeabilization of mitochondrial membranes that accompanies regulated cell death, that is, intrinsic apoptosis as...

Keywords

Adenine Nucleotide Translocase Mitochondrial Carrier Antiporter Activity Permeability Transition Pore Complex Inner Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. Bauer MK, Schubert A, Rocks O, Grimm S. Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis. J Cell Biol. 1999;147:1493–502.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Belzacq-Casagrande A, Martel C, Pertuiset C, Borgne-Sanchez A, Jacotot E, Brenner C. Pharmacological screening and enzymatic assays for apoptosis. Front Biosci. 2009;14:3550–62.CrossRefGoogle Scholar
  3. Brenner C, Cadiou H, Vieira HL, Zamzami N, Marzo I, Xie Z, Leber B, Andrews D, Duclohier H, Reed JC, Kroemer G. Bcl-2 and Bax regulate the channel activity of the mitochondrial adenine nucleotide translocator. Oncogene. 2000;19(3):329–36. https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/10656679.
  4. Brenner C, Moulin C. Physiological roles of the permeability transition pore. Circ Res. 2012;111:1237–47.CrossRefPubMedGoogle Scholar
  5. Brüschweiler S, Yang Q, Run C, Chou JJ. Substrate-modulated ADP/ATP-transporter dynamics revealed by NMR relaxation dispersion. Nat Struct Mol Biol. 2015;22:636–41.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Brustovetsky N, Klingenberg M. Mitochondrial ADP/ATP carrier can be reversibly converted into a large channel by Ca2+. Biochemistry. 1996;35:8483–8.CrossRefPubMedGoogle Scholar
  7. Curcio R, Muto L, Pierri CL, Montalto A, Lauria G, Onofrio A, Fiorillo M, Fiermonte G, Lunetti P, Vozza A, Capobianco L, Cappello AR, Dolce V. New insights about the structural rearrangements required for substrate translocation in the bovine mitochondrial oxoglutarate carrier. Biochim Biophys Acta. 2016;1864:1473–80.CrossRefPubMedGoogle Scholar
  8. Dolce V, Scarcia P, Iacopetta D, Palmieri F. A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue distribution. FEBS Lett. 2005;579:633–7.CrossRefPubMedGoogle Scholar
  9. Dörner A, Schultheiss HP. Adenine nucleotide translocase in the focus of cardiovascular diseases. Trends Cardiovasc Med. 2007;17(8):284–90. https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/18021939.
  10. Gallerne C, Touat Z, Chen ZX, Martel C, Mayola E, Sharaf el dein O, Buron N, Le Bras M, Jacotot E, Borgne Sanchez A, Lemoine A, Lemaire C, Pervaiz S, Brenner C. The fourth isoform of the adenine nucleotide translocator inhibits mitochondrial apoptosis in cancer cells. Int J Biochem Cell Biol. 2010;42:623–9.CrossRefPubMedGoogle Scholar
  11. Halestrap AP, Brenner C. The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Curr Med Chem. 2003;10:1507–25.CrossRefPubMedGoogle Scholar
  12. Klingenberg M. The ADP and ATP transport in mitochondria and its carrier. Biochim Biophys Acta. 2008;1778(10):1978–2021. https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/18510943.
  13. Klumpe I, Savvatis K, Westermann D, Tschöpe C, Rauch U, Landmesser U, Schultheiss HP, Dörner A. Transgenic overexpression of adenine nucleotide translocase 1 protects ischemic hearts against oxidative stress. J Mol Med. 2016;94:645–53.CrossRefPubMedGoogle Scholar
  14. Ko YH, Delannoy M, Hullihen J, Chiu W, Pedersen PL. Mitochondrial ATP synthasome. Cristae-enriched membranes and a multiwell detergent screening assay yield dispersed single complexes containing the ATP synthase and carriers for Pi and ADP/ATP. J Biol Chem. 2003;278:12305–9.CrossRefPubMedGoogle Scholar
  15. Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cal JY, Jones DP, MacGregor GR, Wallace DC. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature. 2004;427:461–5.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Le Bras M, Borgne-Sanchez A, Touat Z, El Dein OS, Deniaud A, Maillier E, Lecellier G, Rebouillat D, Lemaire C, Kroemer G, Jacotot E, Brenner C. Chemosensitization by knockdown of adenine nucleotide translocase-2. Cancer Res. 2006;66:9143–52.CrossRefPubMedGoogle Scholar
  17. Lunetti P, Damiano F, De Benedetto G, Siculella L, Pennetta A, Muto L, Paradies E, Marobbio CM, Dolce V, Capobianco L. Characterization of human and yeast mitochondrial glycine carriers with implications for heme biosynthesis and anemia. J Biol Chem. 2016;291(38):19746–59. https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/27476175.
  18. Marzo I, Brenner C, Zamzami N, Jürgensmeier JM, Susin SA, Vieira HL, Prévost MC, Xie Z, Matsuyama S, Reed JC, Kroemer G. Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science. 1998;281:2027–31.CrossRefPubMedGoogle Scholar
  19. Palmieri F. Mitochondrial transporters of the SLC25 family and associated diseases: a review. J Inherit Metab Dis. 2014;37:565–75.CrossRefPubMedGoogle Scholar
  20. Pebay-Peyroula E, Dahout-Gonzalez C, Kahn R, Trézéguet V, Lauquin GJ, Brandolin G. Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature. 2003;426:39–44.CrossRefPubMedGoogle Scholar
  21. Pfaff E, Klingenberg M. Adenine nucleotide translocation of mitochondria. 1. Specificity and control. Eur J Biochem. 1968;6:66–79.CrossRefPubMedGoogle Scholar
  22. Pietropaolo A, Pierri CL, Palmieri F, Klingenberg M. The switching mechanism of the mitochondrial ADP/ATP carrier explored by free-energy landscapes. Biochim Biophys Acta. 2016;1857:772–81.CrossRefPubMedGoogle Scholar
  23. Rück A, Dolder M, Wallimann T, Brdiczka D. Reconstituted adenine nucleotide translocase forms a channel for small molecules comparable to the mitochondrial permeability transition pore. FEBS Lett. 1998;426:97–101.CrossRefPubMedGoogle Scholar
  24. Wang Y, Ebermann L, Sterner-Kock A, Wika S, Schultheiss HP, Dörner A, Walther T. Myocardial overexpression of adenine nucleotide translocase 1 ameliorates diabetic cardiomyopathy in mice. Exp Physiol. 2009;94:220–7.CrossRefPubMedGoogle Scholar
  25. Weaver JG, Tarze A, Moffat TC, Lebras M, Deniaud A, Brenner C, Bren GD, Morin MY, Phenix BN, Dong L, Jiang SX, Sim VL, Zurakowski B, Lallier J, Hardin H, Wettstein P, van Heeswijk RP, Douen A, Kroemer RT, Hou ST, Bennett SA, Lynch DH, Kroemer G, Badley AD. Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor. J Clin Invest. 2005;115:1828–38.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2016

Authors and Affiliations

  • Grégory Tufo
    • 1
  • Lorenzo Galluzzi
    • 2
    • 3
    • 4
    • 5
  • Guido Kroemer
    • 2
    • 3
    • 4
    • 5
  • Catherine Brenner
    • 1
  1. 1.UMR-S 1180, INSERM, Université Paris-SudChâtenay-MalabryFrance
  2. 2.UMR1138, INSERMParisFrance
  3. 3.Metabolomics PlatformInstitut Gustave RoussyVillejuifFrance
  4. 4.Pôle de BiologieHôpital Européen Georges PompidouParisFrance
  5. 5.Université Paris René DescartesParisFrance