View source for Adenine nucleotide translocator

{{merge|ADP/ATP translocase|date=August 2018}}
{{infobox protein
|Name=solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4
|caption=
|image=
|width=
|HGNCid=10990
|Symbol=[[SLC25A4]]
|AltSymbols=PEO3, PEO2, ANT1
|EntrezGene=291
|OMIM=103220
|RefSeq=NM_001151
|UniProt=P12235
|PDB=
|ECnumber=
|Chromosome=4
|Arm=q
|Band=35
|LocusSupplementaryData=
}}
{{infobox protein
|Name=solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 5
|caption=
|image=
|width=
|HGNCid=10991
|Symbol=SLC25A5
|AltSymbols=ANT2
|EntrezGene=292
|OMIM=300150
|RefSeq=NM_001152
|UniProt=P05141
|PDB=
|ECnumber=
|Chromosome=X
|Arm=q
|Band=24
|LocusSupplementaryData=-q26
}}
{{infobox protein
|Name=solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6
|caption=
|image=
|width=
|HGNCid=10992
|Symbol=[[SLC25A6]]
|AltSymbols=ANT3
|EntrezGene=293
|OMIM=403000
|RefSeq=NM_001636
|UniProt=P12236
|PDB=
|ECnumber=
|Chromosome=Y
|Arm=p
|Band=
|LocusSupplementaryData=
}}
'''Adenine nucleotide translocator''' ('''ANT'''), also known as the [[ADP/ATP translocase]], exchanges free [[Adenosine triphosphate|ATP]] with free [[Adenosine diphosphate|ADP]] across the [[inner mitochondrial membrane]].<ref name="Klingenberg_2008">{{cite journal | vauthors = Klingenberg M | title = The ADP and ATP transport in mitochondria and its carrier | journal = Biochimica et Biophysica Acta | volume = 1778 | issue = 10 | pages = 1978–2021 | date = October 2008 | pmid = 18510943 | doi = 10.1016/j.bbamem.2008.04.011 }}</ref> ANT is the most abundant protein in the [[inner mitochondrial membrane]].<ref name="pmid10926541">{{cite journal | vauthors=Kaukonen J, Juselius JK, Tiranti V, Kyttälä A, Zeviani M, Comi GP, Keränen S, Peltonen L, Suomalainen A | title=Role of adenine nucleotide translocator 1 in mtDNA maintenance | journal= [[Science (journal)|Science]]  | volume=289 | issue=5480 | year=2000 | pages=782–785 | pmid=10926541 | doi=10.1126/science.289.5480.782}}</ref> It belongs to [[mitochondrial carrier]] family.

== Function ==
ANT has long been thought to function asymmetrically as a homodimer of subunits in the inner mitochondrial membrane. The dimer was thought to be a gated pore through which ADP and ATP were exchanged between the mitochondrial matrix and the cytoplasm.  The dimer hypothesis was first challenged when the three-dimensional structure of ANT was discovered to be a monomer.<ref name="pmid14603310">{{cite journal | vauthors = Pebay-Peyroula E, Dahout-Gonzalez C, Kahn R, Trézéguet V, Lauquin GJ, Brandolin G | title = Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside | journal = Nature | volume = 426 | issue = 6962 | pages = 39–44 |date=November 2003| pmid = 14603310 | doi = 10.1038/nature02056 | url = | issn = }}</ref>  Further work has shown that ANT functions as a monomer in detergents<ref name="pmid17572439">{{cite journal | vauthors = Bamber L, Slotboom DJ, Kunji ER | title = Yeast mitochondrial ADP/ATP carriers are monomeric in detergents as demonstrated by differential affinity purification | journal = J. Mol. Biol. | volume = 371 | issue = 2 | pages = 388–95 |date=August 2007| pmid = 17572439 | doi = 10.1016/j.jmb.2007.05.072 | url = | issn = }}</ref> and in mitochondrial membranes.<ref name="pmid17566106">{{cite journal | vauthors = Bamber L, Harding M, Monné M, Slotboom DJ, Kunji ER | title = The yeast mitochondrial ADP/ATP carrier functions as a monomer in mitochondrial membranes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 104 | issue = 26 | pages = 10830–4 |date=June 2007| pmid = 17566106 | pmc = 1891095 | doi = 10.1073/pnas.0703969104 | url = | issn = }}</ref><ref name="pmid20362544">{{cite journal | vauthors = Kunji ER, Crichton PG | title = Mitochondrial carriers function as monomers | journal = Biochim Biophys Acta | volume = 1797| issue = 6–7| pages = 817–831|date=March 2010| pmid = 20362544 | doi = 10.1016/j.bbabio.2010.03.023 }}</ref>

ANT transports the free, i.e. deprotonated, non-[[Magnesium]], non-[[Calcium]] bound forms of [[Adenosine diphosphate|ADP]] and [[Adenosine triphosphate|ATP]], in a 1:1 ratio. It 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.<ref name="pmid20207940">{{cite journal | vauthors = 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 | title = Forward operation of adenine nucleotide translocase during F0F1-ATPase reversal: critical role of matrix substrate-level phosphorylation | journal = FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology | volume = 24 | issue = 7 | pages = 2405–16 | date = July 2010 | pmid = 20207940 | pmc = 2887268 | doi = 10.1096/fj.09-149898 }}</ref><ref name="pmid20207940"/><ref name="pmid21486564">{{cite journal | vauthors = Chinopoulos C | title = Mitochondrial consumption of cytosolic ATP: not so fast | journal = FEBS Letters | volume = 585 | issue = 9 | pages = 1255–9 | date = May 2011 | pmid = 21486564 | doi = 10.1016/j.febslet.2011.04.004 }}</ref><ref name="pmid21541983">{{cite journal | vauthors = Chinopoulos C | title = The "B space" of mitochondrial phosphorylation | journal = Journal of Neuroscience Research | volume = 89 | issue = 12 | pages = 1897–904 | date = December 2011 | pmid = 21541983 | doi = 10.1002/jnr.22659 }}</ref> The ANT and the [[ATP synthase|F0-F1 ATP synthase]] are not necessarily in directional synchrony.<ref name="pmid20207940"/>

Apart from exchange of ADP and ATP across the inner mitochondrial membrane, the ANT also exhibits an intrinsic uncoupling activity<ref name="Klingenberg_2008" /><ref name="pmid7961643">{{cite journal | vauthors = Brustovetsky N, Klingenberg M | title = The reconstituted ADP/ATP carrier can mediate H+ transport by free fatty acids, which is further stimulated by mersalyl | journal = The Journal of Biological Chemistry | volume = 269 | issue = 44 | pages = 27329–36 | date = November 1994 | pmid = 7961643 | doi = }}</ref>

ANT is an important modulatory<ref name="pmid27221760">{{cite journal | vauthors = 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 | title = Alterations in voltage-sensing of the mitochondrial permeability transition pore in ANT1-deficient cells | journal = Scientific Reports | volume = 6 | issue = | pages = 26700 | date = May 2016 | pmid = 27221760 | pmc = 4879635 | doi = 10.1038/srep26700 }}</ref> but not structural<ref name="pmid14749836">{{cite journal | vauthors = Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, MacGregor GR, Wallace DC | title = The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore | journal = Nature | volume = 427 | issue = 6973 | pages = 461–5 | date = January 2004 | pmid = 14749836 | pmc = 3049806 | doi = 10.1038/nature02229 }}</ref> component of the [[mitochondrial permeability transition pore]] which can open and lead to cell death through [[apoptosis]] or [[necrosis]].

== Types ==
In humans, there exist three [[homology (biology)#Paralogy|paraologous]] ANT [[protein isoform|isoforms]]:
* [[SLC25A4]] – found primarily in heart and skeletal muscle
* [[SLC25A5]] – primarily expressed in [[fibroblast]]s
* [[SLC25A6]] – primarily express in liver

==See also==
* [[mitochondrial carrier]]{{clear}}

== References ==
{{Reflist}}

==External links==
* {{MeshName|Adenine+Nucleotide+Translocator+1}}
* {{MeshName|Adenine+Nucleotide+Translocator+2}}
* {{MeshName|Adenine+Nucleotide+Translocator+3}}

{{Membrane transport proteins}}

[[Category:Solute carrier family]]


{{membrane-protein-stub}}