Gene Symbol: Slc25a4
Description: solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 4
Alias: AU019225, Ant1, mANC1, ADP/ATP translocase 1, ADP,ATP carrier protein 1, ADP,ATP carrier protein, heart/skeletal muscle, ANT 1, adenine nucleotide translocase-1, adenine nucleotide translocator 1, skeletal muscle, solute carrier family 25 member 4
Species: mouse
Products:     Slc25a4

Top Publications

  1. Kokoszka J, Waymire K, Levy S, Sligh J, Cai J, Jones D, et al. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature. 2004;427:461-5 pubmed
    ..Moreover, hepatocytes without ANT remained competent to respond to various initiators of cell death. Therefore, ANTs are non-essential structural components of the mtPTP, although they do contribute to its regulation. ..
  2. Lee J, Schriner S, Wallace D. Adenine nucleotide translocator 1 deficiency increases resistance of mouse brain and neurons to excitotoxic insults. Biochim Biophys Acta. 2009;1787:364-70 pubmed publisher
    ..The mouse has three Ant isoforms: Ant1 expressed in heart, muscle, and brain; Ant2 expressed in all tissues but muscle; and Ant4 expressed primarily in ..
  3. Wang K, Long B, Li N, Li L, Liu C, Dong Y, et al. MicroRNA-2861 regulates programmed necrosis in cardiomyocyte by impairing adenine nucleotide translocase 1 expression. Free Radic Biol Med. 2016;91:58-67 pubmed publisher
    ..Here we report that miR-2861 and adenine nucleotide translocase 1 (ANT1) constitute an axis that regulates necrotic cell death in the heart...
  4. Strauss K, Dubiner L, Simon M, ZARAGOZA M, Sengupta P, Li P, et al. Severity of cardiomyopathy associated with adenine nucleotide translocator-1 deficiency correlates with mtDNA haplogroup. Proc Natl Acad Sci U S A. 2013;110:3453-8 pubmed publisher
    ..We studied a 13-generation Mennonite pedigree with autosomal recessive myopathy and cardiomyopathy due to an SLC25A4 frameshift null mutation (c.523delC, p...
  5. Rardin M, Wiley S, Murphy A, Pagliarini D, Dixon J. Dual specificity phosphatases 18 and 21 target to opposing sides of the mitochondrial inner membrane. J Biol Chem. 2008;283:15440-50 pubmed publisher
    ..This work rigorously demonstrates the unique location of two highly similar DSPs on opposing sides of the mitochondrial inner membrane...
  6. Lin Hendel E, McManus M, Wallace D, Anderson S, Golden J. Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders. Cell Rep. 2016;15:229-37 pubmed publisher
    ..Both pharmacologic and genetic inhibition of adenine nucleotide transferase 1 (Ant1) disrupts the non-radial migration of interneurons, but not the radial migration of cortical projection neurons...
  7. Shabalina I, Kramarova T, Nedergaard J, Cannon B. Carboxyatractyloside effects on brown-fat mitochondria imply that the adenine nucleotide translocator isoforms ANT1 and ANT2 may be responsible for basal and fatty-acid-induced uncoupling respectively. Biochem J. 2006;399:405-14 pubmed
    ..However, in liver, only Ant2 mRNA was found, whereas in brown adipose tissue, Ant1 and Ant2 mRNA levels were equal...
  8. Kokoszka J, Waymire K, Flierl A, Sweeney K, Angelin A, MacGregor G, et al. Deficiency in the mouse mitochondrial adenine nucleotide translocator isoform 2 gene is associated with cardiac noncompaction. Biochim Biophys Acta. 2016;1857:1203-1212 pubmed publisher
    ..The predominant isoform is the heart-muscle-brain ANT-isoform gene 1 (Ant1) while the other is the systemic Ant2 gene...
  9. Brand M, Pakay J, Ocloo A, Kokoszka J, Wallace D, Brookes P, et al. The basal proton conductance of mitochondria depends on adenine nucleotide translocase content. Biochem J. 2005;392:353-62 pubmed
    ..We conclude that half to two-thirds of the basal proton conductance of mitochondria is catalysed by the adenine nucleotide carrier, independently of its ATP/ADP exchange or fatty-acid-dependent proton-leak functions. ..

More Information


  1. Mills K, Ellison J, Mathews K. The Ant1 gene maps near Klk3 on proximal mouse chromosome 8. Mamm Genome. 1996;7:707 pubmed
  2. Wang Y, Ebermann L, Sterner Kock A, Wika S, Schultheiss H, Dorner A, et al. Myocardial overexpression of adenine nucleotide translocase 1 ameliorates diabetic cardiomyopathy in mice. Exp Physiol. 2009;94:220-7 pubmed publisher
    ..Our study aimed to test the hypothesis that overexpression of ANT1 in cardiomyocytes has cardioprotective effects in diabetic cardiomyopathy induced by streptozotocin (STZ)...
  3. Chiara F, Castellaro D, Marin O, Petronilli V, BRUSILOW W, Juhaszova M, et al. Hexokinase II detachment from mitochondria triggers apoptosis through the permeability transition pore independent of voltage-dependent anion channels. PLoS ONE. 2008;3:e1852 pubmed publisher
    ..These findings have profound implications for our understanding of the pathways of outer mitochondrial membrane permeabilization and their inactivation in tumors. ..
  4. Buck C, Jurynec M, Gupta D, Law A, Bilger J, Wallace D, et al. Increased adenine nucleotide translocator 1 in reactive astrocytes facilitates glutamate transport. Exp Neurol. 2003;181:149-58 pubmed
    ..we employed an in vivo model of the glial scar and differential display PCR and found an increase in the level of Ant1, a mitochondrial ATP/ADP exchanger that facilitates the flux of ATP out of the mitochondria...
  5. Sharer J, Shern J, Van Valkenburgh H, Wallace D, Kahn R. ARL2 and BART enter mitochondria and bind the adenine nucleotide transporter. Mol Biol Cell. 2002;13:71-83 pubmed
    ..performed on mitochondria isolated from five different tissues from either wild-type or transgenic mice deleted for ANT1. Results confirmed that ANT1 is the predominant binding partner for the BART.ARL2...
  6. Morgan R, Jenkins N, Gilbert D, Copeland N, Balsara B, Testa J, et al. Novel human and mouse annexin A10 are linked to the genome duplications during early chordate evolution. Genomics. 1999;60:40-9 pubmed
  7. Basavalingappa R, Massilamany C, Krishnan B, Gangaplara A, Kang G, Khalilzad Sharghi V, et al. Identification of an Epitope from Adenine Nucleotide Translocator 1 That Induces Inflammation in Heart in A/J Mice. Am J Pathol. 2016;186:3160-3175 pubmed publisher
  8. Yang F, Mo W, Tan B, Wei X, Wang H. Increased frequency of follicular helper T cells in mice viral myocarditis is relevant with anti-ANT antoantibody. Virol J. 2015;12:20 pubmed publisher
    ..Targeting the Tfh cell and IL-21 may be a new therapeutic target for the treatment of CVB3-induced VMC. ..
  9. Roussel J, Thireau J, Brenner C, Saint N, Scheuermann V, Lacampagne A, et al. Palmitoyl-carnitine increases RyR2 oxidation and sarcoplasmic reticulum Ca2+ leak in cardiomyocytes: Role of adenine nucleotide translocase. Biochim Biophys Acta. 2015;1852:749-58 pubmed publisher
  10. Levy S, Chen Y, Graham B, Wallace D. Expression and sequence analysis of the mouse adenine nucleotide translocase 1 and 2 genes. Gene. 2000;254:57-66 pubmed
    ..Mouse Ant1 is expressed at high levels in skeletal muscle and heart, similar to human ANT1...
  11. Lebel M, Leder P. A deletion within the murine Werner syndrome helicase induces sensitivity to inhibitors of topoisomerase and loss of cellular proliferative capacity. Proc Natl Acad Sci U S A. 1998;95:13097-102 pubmed
    ..At the molecular level, wild-type, but not mutant, WS protein copurifies through a series of centrifugation and chromatography steps with a multiprotein DNA replication complex. ..
  12. Grewal P, Bolland D, Todd L, Hewitt J. High-resolution mapping of mouse chromosome 8 identifies an evolutionary chromosomal breakpoint. Mamm Genome. 1998;9:603-7 pubmed
    ..As well as providing clues about chromosomal evolution, this map of the FSHD syntenic mouse region should prove invaluable in the isolation of candidate genes for this disease. ..
  13. Grewal P, van Deutekom J, Mills K, Lemmers R, Mathews K, Frants R, et al. The mouse homolog of FRG1, a candidate gene for FSHD, maps proximal to the myodystrophy mutation on chromosome 8. Mamm Genome. 1997;8:394-8 pubmed
    ..Using a cross segregating the myd mutation and the European Collaborative Interspecific Backcross, we showed that Frg1 maps proximal to the myd locus and to the Clc3 and Ant1 genes.
  14. Martin L, Semenkow S, Hanaford A, Wong M. Mitochondrial permeability transition pore regulates Parkinson's disease development in mutant ?-synuclein transgenic mice. Neurobiol Aging. 2014;35:1132-52 pubmed publisher
    ..Thus, mutant ?Syn transgenic mice on a C57BL/6 background develop PD-like phenotypes, and the mPTP is involved in their disease mechanisms. ..
  15. Cozens A, Runswick M, Walker J. DNA sequences of two expressed nuclear genes for human mitochondrial ADP/ATP translocase. J Mol Biol. 1989;206:261-80 pubmed
    ..The two DNA sequence also contain many short interspersed repetitive sequences including 11 Alu repeats, and a novel element about 236 base-pairs in length, which is repeated in a six-fold tandem array in intron B of the T2 gene. ..
  16. Malorni W, Farrace M, Matarrese P, Tinari A, Ciarlo L, Mousavi Shafaei P, et al. The adenine nucleotide translocator 1 acts as a type 2 transglutaminase substrate: implications for mitochondrial-dependent apoptosis. Cell Death Differ. 2009;16:1480-92 pubmed publisher
    ..the correct assembly and function of the mitochondrial ADP/ATP transporter adenine nucleotide translocator 1 (ANT1)...
  17. Pan S, Wang N, Bisetto S, Yi B, Sheu S. Downregulation of adenine nucleotide translocator 1 exacerbates tumor necrosis factor-α-mediated cardiac inflammatory responses. Am J Physiol Heart Circ Physiol. 2015;308:H39-48 pubmed publisher
    ..We found that adenine nucleotide translocator isoform-1 (ANT1) protein levels were significantly decreased in the inflamed heart of C57BL/6 mice following cecal ligation and ..
  18. Morrow R, Picard M, Derbeneva O, Leipzig J, McManus M, Gouspillou G, et al. Mitochondrial energy deficiency leads to hyperproliferation of skeletal muscle mitochondria and enhanced insulin sensitivity. Proc Natl Acad Sci U S A. 2017;114:2705-2710 pubmed publisher
    ..This was confirmed in mice in which the heart-muscle-brain adenine nucleotide translocator isoform 1 (ANT1) was inactivated...
  19. Loers G, Makhina T, Bork U, Dorner A, Schachner M, Kleene R. The interaction between cell adhesion molecule L1, matrix metalloproteinase 14, and adenine nucleotide translocator at the plasma membrane regulates L1-mediated neurite outgrowth of murine cerebellar neurons. J Neurosci. 2012;32:3917-30 pubmed publisher
    We have identified the adenine nucleotide translocator (ANT) isoforms ANT1 and ANT2 that are present in the plasma membrane of mouse cerebellar neurons as novel binding partners of the cell adhesion molecule L1...
  20. Esposito L, Melov S, Panov A, Cottrell B, Wallace D. Mitochondrial disease in mouse results in increased oxidative stress. Proc Natl Acad Sci U S A. 1999;96:4820-5 pubmed
    ..we examined the mitochondria from mice lacking the heart/muscle isoform of the adenine nucleotide translocator (Ant1), designated Ant1(tm2Mgr) (-/-) mice...
  21. Baines C, Molkentin J. Adenine nucleotide translocase-1 induces cardiomyocyte death through upregulation of the pro-apoptotic protein Bax. J Mol Cell Cardiol. 2009;46:969-77 pubmed
    ..Infection of cultured neonatal cardiomyocytes with an ANT1-encoding adenovirus induced a gene dosage-dependent increase in cell death...
  22. Yu P, Mosbrook D, Tagle D. Genomic organization and expression analysis of mouse kynurenine aminotransferase II, a possible factor in the pathophysiology of Huntington's disease. Mamm Genome. 1999;10:845-52 pubmed
  23. Dron M, Tartare X, Guillo F, Haik S, Barbin G, Maury C, et al. Mouse scrapie responsive gene 1 (Scrg1): genomic organization, physical linkage to sap30, genetic mapping on chromosome 8, and expression in neuronal primary cell cultures. Genomics. 2000;70:140-9 pubmed
    ..histone deacetylase complex, and genetic linkage mapping assigned the localization of Scrg1 to chromosome 8 between Ant1 and Hmg2...
  24. Yin H, Stahl J, Andrade F, McMullen C, Webb Wood S, Newman N, et al. Eliminating the Ant1 isoform produces a mouse with CPEO pathology but normal ocular motility. Invest Ophthalmol Vis Sci. 2005;46:4555-62 pubmed
    The adenine nucleotide transporter 1 gene (ANT1) encodes an inner mitochondrial membrane protein that transports ATP into the cell. Mutations within ANT1 produce a syndrome of chronic progressive external ophthalmoplegia (CPEO) in humans...
  25. Ellison J, Li X, Francke U, Shapiro L. Rapid evolution of human pseudoautosomal genes and their mouse homologs. Mamm Genome. 1996;7:25-30 pubmed
    ..adenine nucleotide translocase-3 (ANT3) gene resulted in the isolation of the murine homologs of the human ANT1 and ANT2 genes...
  26. Grewal P, Hewitt J. Fath, the murine homolog of the Drosophila fat tumor suppressor gene, maps to chromosome 8. Mamm Genome. 1997;8:383-4 pubmed
  27. Devaraju P, Yu J, Eddins D, Mellado Lagarde M, Earls L, Westmoreland J, et al. Haploinsufficiency of the 22q11.2 microdeletion gene Mrpl40 disrupts short-term synaptic plasticity and working memory through dysregulation of mitochondrial calcium. Mol Psychiatry. 2017;22:1313-1326 pubmed publisher
    ..Thus, we propose that mitochondrial calcium deregulation is a novel pathogenic mechanism of cognitive deficiencies in schizophrenia. ..
  28. Bevilacqua L, Seifert E, Estey C, Gerrits M, Harper M. Absence of uncoupling protein-3 leads to greater activation of an adenine nucleotide translocase-mediated proton conductance in skeletal muscle mitochondria from calorie restricted mice. Biochim Biophys Acta. 2010;1797:1389-97 pubmed publisher
    ..Specifically, they imply the potential for an interaction, or some degree of functional redundancy, between UCP3 and ANT, and also suggest that UCP3 can minimize the induction of the ANT-mediated 'energy-wasting' process during CR...
  29. Subramaniam V, Golik P, Murdock D, Levy S, Kerstann K, Coskun P, et al. MITOCHIP assessment of differential gene expression in the skeletal muscle of Ant1 knockout mice: coordinate regulation of OXPHOS, antioxidant, and apoptotic genes. Biochim Biophys Acta. 2008;1777:666-75 pubmed publisher
    Genetic inactivation of the nuclear-encoded mitochondrial heart-muscle adenine nucleotide translocator-1 (ANT1), which exports mitochondrial ATP to the cytosol in both humans (ANT1-/-) and mice (Ant1-/-), results in lactic acidosis and ..
  30. Nadtochiy S, Zhu Q, Zhu Q, Urciuoli W, Rafikov R, Black S, et al. Nitroalkenes confer acute cardioprotection via adenine nucleotide translocase 1. J Biol Chem. 2012;287:3573-80 pubmed publisher
    ..Mild uncoupling of mitochondria is known to be cardioprotective, and adenine nucleotide translocase 1 (ANT1) is a key mediator of mitochondrial uncoupling...
  31. Echtay K, Esteves T, Pakay J, Jekabsons M, Lambert A, Portero Otin M, et al. A signalling role for 4-hydroxy-2-nonenal in regulation of mitochondrial uncoupling. EMBO J. 2003;22:4103-10 pubmed
    ..Our findings indicate that hydroxynonenal is not merely toxic, but may be a biological signal to induce uncoupling through UCPs and ANT and thus decrease mitochondrial ROS production. ..
  32. Zhuge J, Cederbaum A. Inhibition of the mitochondrial permeability transition by cyclosporin A prevents pyrazole plus lipopolysaccharide-induced liver injury in mice. Free Radic Biol Med. 2009;46:406-13 pubmed publisher
    ..These results indicate that mitochondria are the critical targets of pyrazole plus LPS in mediating liver injury...
  33. Graham B, Waymire K, Cottrell B, Trounce I, MacGregor G, Wallace D. A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator. Nat Genet. 1997;16:226-34 pubmed
    ..disease, we generated 'knockout' mice deficient in the heart/muscle isoform of the adenine nucleotide translocator (Ant1)...
  34. Phillips M, Webb Wood S, Faulkner A, Jabbar S, Biousse V, Newman N, et al. Retinal function and structure in Ant1-deficient mice. Invest Ophthalmol Vis Sci. 2010;51:6744-52 pubmed publisher
    ..Because of the high metabolic demands of the retina, the authors examined whether elimination of the Ant1 isoform in a transgenic mouse affects retinal function or morphology...
  35. Lynn E, Stevens M, Wong R, Carabenciov D, Jacobson J, Murphy E, et al. Transient upregulation of PGC-1alpha diminishes cardiac ischemia tolerance via upregulation of ANT1. J Mol Cell Cardiol. 2010;49:693-8 pubmed publisher
    ..controls. Affymetrix gene array analysis showed a 3-fold PGC-1alpha-mediated upregulation of adenine nucleotide translocase 1 (ANT1)...
  36. Forlani G, Giarda E, Ala U, Di Cunto F, Salani M, Tupler R, et al. The MeCP2/YY1 interaction regulates ANT1 expression at 4q35: novel hints for Rett syndrome pathogenesis. Hum Mol Genet. 2010;19:3114-23 pubmed publisher
    ..We show that MeCP2 cooperates with YY1 in repressing the ANT1 gene encoding a mitochondrial adenine nucleotide translocase...