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Adenine nucleotide translocator (ANT), also known as the ADP/ATP translocase or mitochondrial ADP/ATP carrier, exchanges free ATP with free ADP across the inner mitochondrial membrane.[1][2] ANT is the most abundant protein in the inner mitochondrial membrane and belongs to mitochondrial carrier family.[3]

solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4
Alt. symbolsPEO3, PEO2, ANT1
Other data
LocusChr. 4 q35
solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 5
Alt. symbolsANT2
Other data
LocusChr. X q24-q26
solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6
Alt. symbolsANT3
Other data
LocusChr. Y p



ANT has long been thought to function as a homodimer, but this concept was challenged by the projection structure of the yeast Aac3p solved by electron crystallography, which showed that the protein was three-fold symmetric and monomeric, with the translocation pathway for the substrate through the centre.[4] The atomic structure of the bovine ANT confirmed this notion, and provided the first structural fold of a mitochondrial carrier[5]. Further work has demonstrated that ANT is a monomer in detergents [6] and functions as a monomer in mitochondrial membranes.[7][8]

ANT transports the free, i.e. deprotonated, non-Magnesium, non-Calcium bound forms of ADP and ATP, in a 1:1 ratio.[1] Transport is fully reversible, and its directionality is governed by the concentrations of its substrates (ADP and ATP inside and outside mitochondria), the chelators of the adenine nucleotides, and the mitochondrial membrane potential. The relationship of these parameters can be expressed by an equation solving for the 'reversal potential of the ANT" (Erev_ANT), a value of the mitochondrial membrane potential at which no net transport of adenine nucleotides takes place by the ANT.[9][10][11] The ANT and the F0-F1 ATP synthase are not necessarily in directional synchrony.[9]

Apart from exchange of ADP and ATP across the inner mitochondrial membrane, the ANT also exhibits an intrinsic uncoupling activity[1][12]

ANT is an important modulatory[13] but not structural[14] component of the mitochondrial permeability transition pore which can open and lead to cell death through apoptosis or necrosis.

The translocator cycles between two states, called the cytoplasmic and matrix state, opening up to these compartments in an alternating way.[1][2] There are structures available that show the translocator locked in a cytoplasmic state by the inhibitor carboxyatractyloside[5][15], or in the matrix state by the inhibitor bongkrekic acid.[16]


In humans, there exist three paraologous ANT isoforms:

See alsoEdit


  1. ^ a b c d Klingenberg M (October 2008). "The ADP and ATP transport in mitochondria and its carrier". Biochimica et Biophysica Acta. 1778 (10): 1978–2021. doi:10.1016/j.bbamem.2008.04.011. PMID 18510943.
  2. ^ a b Kunji ER, Aleksandrova A, King MS, Majd H, Ashton VL, Cerson E, Springett R, Kibalchenko M, Tavoulari S, Crichton PG, Ruprecht JJ (October 2016). "The transport mechanism of the mitochondrial ADP/ATP carrier". Biochimica et Biophysica Acta. Channels and transporters in cell metabolism. 1863 (10): 2379–93. doi:10.1016/j.bbamcr.2016.03.015. PMID 27001633.
  3. ^ Palmieri F, Monné M (October 2016). "Discoveries, metabolic roles and diseases of mitochondrial carriers: A review". Biochimica et Biophysica Acta. Channels and transporters in cell metabolism. 1863 (10): 2362–78. doi:10.1016/j.bbamcr.2016.03.007. PMID 26968366.
  4. ^ Kunji ER, Harding M (September 2003). "Projection structure of the atractyloside-inhibited mitochondrial ADP/ATP carrier of Saccharomyces cerevisiae". The Journal of Biological Chemistry. 278 (39): 36985–8. doi:10.1074/jbc.C300304200. PMID 12893834.
  5. ^ a b Pebay-Peyroula E, Dahout-Gonzalez C, Kahn R, Trézéguet V, Lauquin GJ, Brandolin G (November 2003). "Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside". Nature. 426 (6962): 39–44. doi:10.1038/nature02056. PMID 14603310.
  6. ^ Bamber L, Slotboom DJ, Kunji ER (August 2007). "Yeast mitochondrial ADP/ATP carriers are monomeric in detergents as demonstrated by differential affinity purification". Journal of Molecular Biology. 371 (2): 388–95. doi:10.1016/j.jmb.2007.05.072. PMID 17572439.
  7. ^ Bamber L, Harding M, Monné M, Slotboom DJ, Kunji ER (June 2007). "The yeast mitochondrial ADP/ATP carrier functions as a monomer in mitochondrial membranes". Proceedings of the National Academy of Sciences of the United States of America. 104 (26): 10830–4. doi:10.1073/pnas.0703969104. PMC 1891095. PMID 17566106.
  8. ^ Kunji ER, Crichton PG (March 2010). "Mitochondrial carriers function as monomers". Biochimica et Biophysica Acta. 1797 (6–7): 817–31. doi:10.1016/j.bbabio.2010.03.023. PMID 20362544.
  9. ^ a b Chinopoulos C, Gerencser AA, Mandi M, Mathe K, Töröcsik B, Doczi J, Turiak L, Kiss G, Konràd C, Vajda S, Vereczki V, Oh RJ, Adam-Vizi V (July 2010). "Forward operation of adenine nucleotide translocase during F0F1-ATPase reversal: critical role of matrix substrate-level phosphorylation". FASEB Journal. 24 (7): 2405–16. doi:10.1096/fj.09-149898. PMC 2887268. PMID 20207940.
  10. ^ Chinopoulos C (May 2011). "Mitochondrial consumption of cytosolic ATP: not so fast". FEBS Letters. 585 (9): 1255–9. doi:10.1016/j.febslet.2011.04.004. PMID 21486564.
  11. ^ Chinopoulos C (December 2011). "The "B space" of mitochondrial phosphorylation". Journal of Neuroscience Research. 89 (12): 1897–904. doi:10.1002/jnr.22659. PMID 21541983.
  12. ^ Brustovetsky N, Klingenberg M (November 1994). "The reconstituted ADP/ATP carrier can mediate H+ transport by free fatty acids, which is further stimulated by mersalyl". The Journal of Biological Chemistry. 269 (44): 27329–36. PMID 7961643.
  13. ^ Doczi J, Torocsik B, Echaniz-Laguna A, Mousson de Camaret B, Starkov A, Starkova N, Gál A, Molnár MJ, Kawamata H, Manfredi G, Adam-Vizi V, Chinopoulos C (May 2016). "Alterations in voltage-sensing of the mitochondrial permeability transition pore in ANT1-deficient cells". Scientific Reports. 6: 26700. doi:10.1038/srep26700. PMC 4879635. PMID 27221760.
  14. ^ Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, MacGregor GR, Wallace DC (January 2004). "The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore". Nature. 427 (6973): 461–5. doi:10.1038/nature02229. PMC 3049806. PMID 14749836.
  15. ^ Ruprecht JJ, Hellawell AM, Harding M, Crichton PG, McCoy AJ, Kunji ER (January 2014). "Structures of yeast mitochondrial ADP/ATP carriers support a domain-based alternating-access transport mechanism". Proceedings of the National Academy of Sciences of the United States of America. 111 (4): E426–34. doi:10.1073/pnas.1320692111. PMC 3910652. PMID 24474793.
  16. ^ Ruprecht JJ, King MS, Zögg T, Aleksandrova AA, Pardon E, Crichton PG, Steyaert J, Kunji ER (January 2019). "The Molecular Mechanism of Transport by the Mitochondrial ADP/ATP Carrier". Cell. 176 (3): 435–447.e15. doi:10.1016/j.cell.2018.11.025. PMC 6349463. PMID 30611538.

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