adenine nucleotide translocator 2


Summary: A subtype of mitochondrial ADP, ATP translocase found primarily in FIBROBLASTS.

Top Publications

  1. De Marcos Lousa C, Trezeguet V, Dianoux A, Brandolin G, Lauquin G. The human mitochondrial ADP/ATP carriers: kinetic properties and biogenesis of wild-type and mutant proteins in the yeast S. cerevisiae. Biochemistry. 2002;41:14412-20 pubmed
    ..These results point to the importance of the N-terminal region of HAnc1p for its biogenesis and transport activity in yeast mitochondria. ..
  2. Luciakova K, Barath P, Poliakova D, Persson A, Nelson B. Repression of the human adenine nucleotide translocase-2 gene in growth-arrested human diploid cells: the role of nuclear factor-1. J Biol Chem. 2003;278:30624-33 pubmed
    ..Thus, enhanced binding of NF1 is a key step in the growth arrest repression of ANT2 transcription. To our knowledge, this is the first report showing a role for NF1 in growth arrest. ..
  3. Jang J, Kim M, Jeon Y, Joung Y, Park K, Kim C. Adenovirus adenine nucleotide translocator-2 shRNA effectively induces apoptosis and enhances chemosensitivity by the down-regulation of ABCG2 in breast cancer stem-like cells. Exp Mol Med. 2012;44:251-9 pubmed publisher
    ..Our results suggest that ANT2 suppression by adeno-shRNA virus is an effective strategy to induce cell death and increase the chemosensitivity of stem-like cells in breast cancer. ..
  4. Choi Y, Jeon Y, Jang J, Chung J, Kim C. Treatment with mANT2 shRNA enhances antitumor therapeutic effects induced by MUC1 DNA vaccination. Mol Ther. 2011;19:979-89 pubmed publisher
    ..These results suggest that combined therapy enhances antitumor activity, and that it offers an effective antitumor strategy for treating melanoma...
  5. Jang J, Jeon Y, Choi Y, Kim C. Short-hairpin RNA-induced suppression of adenine nucleotide translocase-2 in breast cancer cells restores their susceptibility to TRAIL-induced apoptosis by activating JNK and modulating TRAIL receptor expression. Mol Cancer. 2010;9:262 pubmed publisher
    ..Co-treatment with ANT2 shRNA and TRAIL efficiently suppressed tumor growth in these mice. ANT2 suppression by shRNA might be exploited to overcome TRAIL-resistance in cancer. ..
  6. 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. ..
  7. Sharaf el Dein O, Mayola E, Chopineau J, Brenner C. The adenine nucleotide translocase 2, a mitochondrial target for anticancer biotherapy. Curr Drug Targets. 2011;12:894-901 pubmed
  8. Chevrollier A, Loiseau D, Gautier F, Malthiery Y, Stepien G. ANT2 expression under hypoxic conditions produces opposite cell-cycle behavior in 143B and HepG2 cancer cells. Mol Carcinog. 2005;42:1-8 pubmed
    ..This loss of cell dependence on oxidative metabolism is an important factor in the development of tumors. ..
  9. Chevrollier A, Loiseau D, Reynier P, Stepien G. Adenine nucleotide translocase 2 is a key mitochondrial protein in cancer metabolism. Biochim Biophys Acta. 2011;1807:562-7 pubmed publisher
    ..Since the expression of ANT2 is closely linked to the mitochondrial bioenergetics of tumors, it should be taken into account for individualizing cancer treatments and for the development of anticancer strategies. ..

More Information


  1. Chevrollier A, Loiseau D, Stepien G. [What is the specific role of ANT2 in cancer cells?]. Med Sci (Paris). 2005;21:156-61 pubmed
  2. Jang J, Jeon Y, Kim C. Degradation of HER2/neu by ANT2 shRNA suppresses migration and invasiveness of breast cancer cells. BMC Cancer. 2010;10:391 pubmed publisher
  3. Jang J, Choi Y, Jeon Y, Kim C. Suppression of adenine nucleotide translocase-2 by vector-based siRNA in human breast cancer cells induces apoptosis and inhibits tumor growth in vitro and in vivo. Breast Cancer Res. 2008;10:R11 pubmed publisher
    ..Ultimately, ANT2 shRNA effectively inhibited tumor growth in vivo. These results suggest that vector-based ANT2 RNA interference could be an efficient molecular therapeutic method for breast cancer with high expression of ANT2. ..
  4. Chevrollier A, Loiseau D, Chabi B, Renier G, Douay O, Malthiery Y, et al. ANT2 isoform required for cancer cell glycolysis. J Bioenerg Biomembr. 2005;37:307-16 pubmed
  5. 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
    ..The data are therefore compatible with a tentative model in which the ANT2 isoform mediates fatty-acid-induced uncoupling, whereas the ANT1 isoform may mediate a significant part of the high basal proton leak in brown-fat mitochondria. ..
  6. Le Bras M, Borgne Sanchez A, Touat Z, El Dein O, Deniaud A, Maillier E, et al. Chemosensitization by knockdown of adenine nucleotide translocase-2. Cancer Res. 2006;66:9143-52 pubmed
    ..These data identify ANT2 as an endogenous inhibitor of MMP and suggest that its selective inhibition could constitute a promising strategy of chemosensitization. ..
  7. Lu A, Lv B, Qiu F, Wang X, Cao X. Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma. Oncol Rep. 2017;37:2071-2078 pubmed publisher
    ..Moreover, we demonstrated that high-intensity focused ultrasound (HIFU) in unresectable HCC upregulated serum miR-137. Combining HIFU and sorafenib may be a wise option for advanced and unresectable HCC. ..
  8. Zamzami N, Larochette N, Kroemer G. Mitochondrial permeability transition in apoptosis and necrosis. Cell Death Differ. 2005;12 Suppl 2:1478-80 pubmed
  9. Clémençon B, Babot M, Trezeguet V. The mitochondrial ADP/ATP carrier (SLC25 family): pathological implications of its dysfunction. Mol Aspects Med. 2013;34:485-93 pubmed publisher
  10. Oishi M, Iizumi Y, Taniguchi T, Goi W, Miki T, Sakai T. Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2. PLoS ONE. 2013;8:e55922 pubmed publisher
    ..These results suggest that apigenin upregulates DR5 and enhances Apo2L/TRAIL-induced apoptosis by binding and inhibiting ANT2. We propose that ANT2 inhibitors may contribute to Apo2L/TRAIL therapy. ..
  11. Rodriguez N, Yang J, Hasselblatt K, Liu S, Zhou Y, Rauh Hain J, et al. Casein kinase I epsilon interacts with mitochondrial proteins for the growth and survival of human ovarian cancer cells. EMBO Mol Med. 2012;4:952-63 pubmed publisher
  12. 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
    ..Thus, our results indicate that plasma membrane-localized ANT1 and ANT2 regulate L1-mediated neurite outgrowth in conjunction with MMP14. ..
  13. Barath P, Poliakova D, Luciakova K, Nelson B. Identification of NF1 as a silencer protein of the human adenine nucleotide translocase-2 gene. Eur J Biochem. 2004;271:1781-8 pubmed
    ..Our data support the belief that NF1 acts as a repressor when bound to silencing Site-2 and Site-3 of the ANT2 gene. ..
  14. Kim H, Je J, Son T, Park H, Ji S, Pokharel Y, et al. The hepatoprotective effects of adenine nucleotide translocator-2 against aging and oxidative stress. Free Radic Res. 2012;46:21-9 pubmed publisher
  15. Luciakova K, Kollarovic G, Kretova M, Sabova L, Nelson B. TGF-? signals the formation of a unique NF1/Smad4-dependent transcription repressor-complex in human diploid fibroblasts. Biochem Biophys Res Commun. 2011;411:648-53 pubmed publisher
    ..The present finding that NF1/Smad4 repressor complexes are formed through TGF-? signaling pathways suggests a new, but much broader, role for these complexes in the initiation or maintenance of the growth-inhibited state. ..
  16. Zamora M, Meroño C, Viñas O, Mampel T. Recruitment of NF-kappaB into mitochondria is involved in adenine nucleotide translocase 1 (ANT1)-induced apoptosis. J Biol Chem. 2004;279:38415-23 pubmed
    ..Thus, we propose that the mitochondrial recruitment of NF-kappaB observed following ANT1 overexpression has an important role in ANT1 proapoptotic activity. ..
  17. De Marcos Lousa C, Trezeguet V, David C, Postis V, Arnou B, Pebay Peyroula E, et al. Valine 181 is critical for the nucleotide exchange activity of human mitochondrial ADP/ATP carriers in yeast. Biochemistry. 2005;44:4342-8 pubmed
    ..These results are discussed in the light of the bovine Ancp structure, that shares more than 90% amino acid identity with Hancps, and its interaction with the lipid environment. ..
  18. Dorner A, Giessen S, Gaub R, Grosse Siestrup H, Schwimmbeck P, Hetzer R, et al. An isoform shift in the cardiac adenine nucleotide translocase expression alters the kinetic properties of the carrier in dilated cardiomyopathy. Eur J Heart Fail. 2006;8:81-9 pubmed
    ..90.4 +/- 2.9 microM in controls (p < 0.03). The altered isoform expression in DCM hearts entails changes in the kinetic properties of total ANT protein restricting ANT function and contributing to disturbed energy metabolism in DCM. ..
  19. Yang L, He Y, Kong Q, Zhang W, Xi D, Mao H, et al. Isolation, nucleotide identification and tissue expression of three novel ovine genes-SLC25A4, SLC25A5 and SLC25A6. Mol Biol Rep. 2010;37:2743-8 pubmed publisher
    ..Our experiment is the first to provide the primary foundation for further insight into these three sheep genes. ..
  20. Porra V, Ferraro Peyret C, Durand C, Selmi Ruby S, Giroud H, Berger Dutrieux N, et al. Silencing of the tumor suppressor gene SLC5A8 is associated with BRAF mutations in classical papillary thyroid carcinomas. J Clin Endocrinol Metab. 2005;90:3028-35 pubmed
    ..These data identify a relationship between the methylation-associated silencing of the tumor-suppressor gene SLC5A8 and the T1796A point mutation of the BRAF gene in the PTC-cf. subtype of thyroid carcinomas. ..
  21. Skarka L, Bardova K, Brauner P, Flachs P, Jarkovská D, Kopecky J, et al. Expression of mitochondrial uncoupling protein 3 and adenine nucleotide translocase 1 genes in developing rat heart: putative involvement in control of mitochondrial membrane potential. J Mol Cell Cardiol. 2003;35:321-30 pubmed
    ..The results support the view that mitochondrial energy conversion in heart changes during ontogeny and suggest the involvement of UCP3 and/or ANT1 in the control mechanism. ..
  22. Liu Y, Pu Q, Wu M, Yu C. Proteomic analysis for the impact of hypercholesterolemia on expressions of hepatic drug transporters and metabolizing enzymes. Xenobiotica. 2016;46:940-7 pubmed publisher
    ..Especially, decreased function of LXRα contributes to the reduced expressions of MRP2 and OAT2. ..
  23. Vandewalle J, Bauters M, Van Esch H, Belet S, Verbeeck J, Fieremans N, et al. The mitochondrial solute carrier SLC25A5 at Xq24 is a novel candidate gene for non-syndromic intellectual disability. Hum Genet. 2013;132:1177-85 pubmed publisher
    ..Our data indicate that SLC25A5 is involved in memory formation or establishment, which could add mitochondrial processes to the wide array of pathways that regulate normal cognitive functions. ..
  24. Choi Y, Lee H, Lee J, Jeon Y. The combination of ANT2 shRNA and hNIS radioiodine gene therapy increases CTL cytotoxic activity through the phenotypic modulation of cancer cells: combination treatment with ANT2 shRNA and I-131. BMC Cancer. 2013;13:143 pubmed publisher
    ..Our results suggest that combination therapy can be used as a new therapeutic strategy for cancer patients who show resistance to single therapy such as radiation or immunotherapy. ..
  25. Luciakova K, Kollarovic G, Barath P, Nelson B. Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex. Biochem J. 2008;412:123-30 pubmed publisher
    ..These findings suggest a possible functional relationship between the NF1 and Smad proteins that has not been previously observed. ..
  26. Jang J, Lee Y, Jeon Y, Lee K, Jang J, Kim C. ANT2 suppression by shRNA restores miR-636 expression, thereby downregulating Ras and inhibiting tumorigenesis of hepatocellular carcinoma. Exp Mol Med. 2013;45:e3 pubmed publisher
    ..The data suggest that miR-636 might function as a tumor suppressor miRNA affecting HCC tumorigenesis via downregulation of Ras, and that ANT2 suppression by shRNA could exert an anticancer effect by restoring miR-636 expression in HCC. ..
  27. Park J, Kim S, Baek M, Park T, Lim I, Seo Y, et al. B-cell translocation gene 2: expression in the rat ovary and potential association with adenine nucleotide translocase 2 in mitochondria. Mol Cell Endocrinol. 2013;367:31-40 pubmed publisher
    ..These findings demonstrate the gonadotropin stimulation of Btg2 in the ovary and, the physical interaction of Btg2 with Ant2 in mitochondria. ..
  28. Dupont P, Guttin A, Issartel J, Stepien G. Computational identification of transcriptionally co-regulated genes, validation with the four ANT isoform genes. BMC Genomics. 2012;13:482 pubmed publisher
    ..Moreover, this computational strategy on the study of regulatory pathways should provide, along with transcriptomics and metabolomics, data to construct cellular metabolic networks. ..
  29. Kuramori C, Azuma M, Kume K, Kaneko Y, Inoue A, Yamaguchi Y, et al. Capsaicin binds to prohibitin 2 and displaces it from the mitochondria to the nucleus. Biochem Biophys Res Commun. 2009;379:519-25 pubmed publisher
    ..This work will serve as an important foundation for further understanding of anticancer activity of capsaicin. ..
  30. Kashiwaya K, Hosokawa M, Eguchi H, Ohigashi H, Ishikawa O, Shinomura Y, et al. Identification of C2orf18, termed ANT2BP (ANT2-binding protein), as one of the key molecules involved in pancreatic carcinogenesis. Cancer Sci. 2009;100:457-64 pubmed publisher
    ..These findings implicated that C2orf18, termed ANT2-binding protein (ANT2BP), might serve as a candidate molecular target for pancreatic cancer therapy. ..
  31. Moro L, Arbini A, Hsieh J, Ford J, Simpson E, Hajibeigi A, et al. Aromatase deficiency inhibits the permeability transition in mouse liver mitochondria. Endocrinology. 2010;151:1643-52 pubmed publisher
  32. Lim C, Hamazaki T, Braun E, Wade J, Terada N. Evolutionary genomics implies a specific function of Ant4 in mammalian and anole lizard male germ cells. PLoS ONE. 2011;6:e23122 pubmed publisher
    ..Taken together with the fact that Ant4 protein has a uniquely conserved structure when compared to other somatic Ant1, 2 and 3, there may be a specific advantage for mammals and lizards to express Ant4 in their male germ cells...
  33. Kharenko O, Boyd J, Nelson K, Abrams S, Loewen M. Identification and characterization of interactions between abscisic acid and mitochondrial adenine nucleotide translocators. Biochem J. 2011;437:117-23 pubmed publisher
  34. Ito S, Tan L, Andoh D, Narita T, Seki M, Hirano Y, et al. MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation. Mol Cell. 2010;39:632-40 pubmed publisher
  35. van Wietmarschen N, Moradian A, Morin G, Lansdorp P, Uringa E. The mammalian proteins MMS19, MIP18, and ANT2 are involved in cytoplasmic iron-sulfur cluster protein assembly. J Biol Chem. 2012;287:43351-8 pubmed publisher
    ..Together, these results elucidate the composition and interactions within the late CIA complex. ..
  36. Jang J, Jeon Y, Lee C, Kim C. ANT2 suppression by shRNA may be able to exert anticancer effects in HCC further by restoring SOCS1 expression. Int J Oncol. 2013;42:574-82 pubmed publisher
    ..ANT2 suppression by shRNA may be able to exert anticancer effects in HCC further by restoring SOCS1 expression. ..
  37. Bellanti F, Romano A, Giudetti A, Rollo T, Blonda M, Tamborra R, et al. Many faces of mitochondrial uncoupling during age: damage or defense?. J Gerontol A Biol Sci Med Sci. 2013;68:892-902 pubmed publisher
    ..This does not occur in liver, where ATP depletion and oxidative stress may stimulate mitochondrial biogenesis and eliminate damaged cells. ..
  38. Tanaka M, Sata T, Kawaguchi Y. The product of the Herpes simplex virus 1 UL7 gene interacts with a mitochondrial protein, adenine nucleotide translocator 2. Virol J. 2008;5:125 pubmed publisher
    ..Using mass spectrometry-based proteomics technology, we identified a cellular mitochondrial protein, adenine nucleotide translocator 2 (ANT2), as a UL7-interacting partner...
  39. Kim J, Hwang M, Lee H, Lee S, Lee J, Ahn B. Combined RNA interference of adenine nucleotide translocase-2 and ganciclovir therapy in hepatocellular carcinoma. Nucl Med Biol. 2013;40:987-93 pubmed publisher
    ..Therefore it could be applied treating incurable hepatocellular carcinoma. ..
  40. Ho L, Titus A, Banerjee K, George S, Lin W, Deota S, et al. SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK. Aging (Albany NY). 2013;5:835-49 pubmed
    ..We find that Sirt4 affects mitochondrial uncoupling via the adenine nucleotide translocator 2 (ANT2)...
  41. Lee Y, Kim J, Osborne O, Oh D, Sasik R, Schenk S, et al. Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity. Cell. 2014;157:1339-52 pubmed publisher
    ..These results reveal the sequential series of events in obesity-induced inflammation and insulin resistance. ..
  42. Baik S, Lee J, Lee Y, Jang J, Kim C. ANT2 shRNA downregulates miR-19a and miR-96 through the PI3K/Akt pathway and suppresses tumor growth in hepatocellular carcinoma cells. Exp Mol Med. 2016;48:e222 pubmed publisher
  43. Jacques C, Baris O, Prunier Mirebeau D, Savagner F, Rodien P, Rohmer V, et al. Two-step differential expression analysis reveals a new set of genes involved in thyroid oncocytic tumors. J Clin Endocrinol Metab. 2005;90:2314-20 pubmed
    ..Our results show an increased expression of genes involved in protein metabolism in oncocytoma, the significance of which requires investigation. ..