Adenine nucleotide translocator: Difference between revisions

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{{merge|ADP/ATP translocase|date=August 2018}}
{{infobox protein
{{infobox protein
|Name=solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4
|Name=solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4
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|LocusSupplementaryData=
|LocusSupplementaryData=
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}}
'''Adenine nucleotide translocator''' ('''ANT'''), also known as the [[adenosine diphosphate|ADP]]/[[Adenosine triphosphate|ATP]] translocator, exports [[Adenosine triphosphate|ATP]] from the [[mitochondrial matrix]] and imports [[Adenosine diphosphate|ADP]] into the matrix.<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 | url = http://www.sciencemag.org/content/289/5480/782.long | id= | pmid=10926541 | doi=10.1126/science.289.5480.782}}</ref> ANT is the most plentiful protein in the [[inner mitochondrial membrane]].<ref name="pmid10926541" />
'''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 ==
== 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 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 is an important structural component of the [[mitochondrial permeability transition pore]]<ref name="pmid10926541" />{{irrelevant citation|date=October 2013|reason=source discusses mtDNA maintenance; PTP is now believed to be from ATP synthase}} which can open and lead to cell death through [[apoptosis]] or [[necrosis]].
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 ==
== Types ==
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==See also==
==See also==
* [[mitochondrial carrier]]
* [[mitochondrial carrier]]{{clear}}


==Footnotes==
== References ==
{{Reflist}}
{{Reflist}}


Latest revision as of 08:11, 9 January 2019

solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4
Identifiers
SymbolSLC25A4
Alt. symbolsPEO3, PEO2, ANT1
Entrez291
HUGO10990
OMIM103220
RefSeqNM_001151
UniProtP12235
Other data
LocusChr. 4 q35
solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 5
Identifiers
SymbolSLC25A5
Alt. symbolsANT2
Entrez292
HUGO10991
OMIM300150
RefSeqNM_001152
UniProtP05141
Other data
LocusChr. X q24-q26
solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6
Identifiers
SymbolSLC25A6
Alt. symbolsANT3
Entrez293
HUGO10992
OMIM403000
RefSeqNM_001636
UniProtP12236
Other data
LocusChr. Y p

Adenine nucleotide translocator (ANT), also known as the ADP/ATP translocase, exchanges free ATP with free ADP across the inner mitochondrial membrane.[1] ANT is the most abundant protein in the inner mitochondrial membrane.[2] 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.[3] Further work has shown that ANT functions as a monomer in detergents[4] and in mitochondrial membranes.[5][6]

ANT transports the free, i.e. deprotonated, non-Magnesium, non-Calcium bound forms of ADP and 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.[7][7][8][9] The ANT and the F0-F1 ATP synthase are not necessarily in directional synchrony.[7]

Apart from exchange of ADP and ATP across the inner mitochondrial membrane, the ANT also exhibits an intrinsic uncoupling activity[1][10]

ANT is an important modulatory[11] but not structural[12] 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 paraologous ANT isoforms:

See also

References

  1. ↑ 1.0 1.1 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. ↑ Kaukonen J, Juselius JK, Tiranti V, Kyttälä A, Zeviani M, Comi GP, Keränen S, Peltonen L, Suomalainen A (2000). "Role of adenine nucleotide translocator 1 in mtDNA maintenance". Science. 289 (5480): 782–785. doi:10.1126/science.289.5480.782. PMID 10926541.
  3. ↑ 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.
  4. ↑ Bamber L, Slotboom DJ, Kunji ER (August 2007). "Yeast mitochondrial ADP/ATP carriers are monomeric in detergents as demonstrated by differential affinity purification". J. Mol. Biol. 371 (2): 388–95. doi:10.1016/j.jmb.2007.05.072. PMID 17572439.
  5. ↑ 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". Proc. Natl. Acad. Sci. U.S.A. 104 (26): 10830–4. doi:10.1073/pnas.0703969104. PMC 1891095. PMID 17566106.
  6. ↑ Kunji ER, Crichton PG (March 2010). "Mitochondrial carriers function as monomers". Biochim Biophys Acta. 1797 (6–7): 817–831. doi:10.1016/j.bbabio.2010.03.023. PMID 20362544.
  7. ↑ 7.0 7.1 7.2 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 : Official Publication of the Federation of American Societies for Experimental Biology. 24 (7): 2405–16. doi:10.1096/fj.09-149898. PMC 2887268. PMID 20207940.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.

External links


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