Affinage

SLC25A5

ADP/ATP translocase 2 · UniProt P05141

Length
298 aa
Mass
32.9 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC25A5 (ANT2) is a mitochondrial inner membrane ADP/ATP translocase whose preferential import of glycolytic ATP into mitochondria sustains mitochondrial membrane potential and integrity in highly proliferative, transformed, and respiration-deficient cells (PMID:16341775, PMID:15486956). Functional complementation in yeast established that human ANT2 specifically supports growth under anaerobic conditions, consistent with an ATP-importing rather than ATP-exporting directionality (PMID:16341775), and this ATP-import activity blunts membrane hyperpolarization and limits cell death during hypoxia-reoxygenation (PMID:33255741). ANT2 expression is tightly controlled at the transcriptional level: Sp1 acts bidirectionally through GC-box elements, with distal A/B boxes activating and a C box adjacent to the start site repressing transcription via positional interaction between Sp1 complexes (PMID:8702555, PMID:11683873), while TGF-β-driven NF1/Smad4 repressor complexes silence ANT2 during replicative, oncogene-induced, drug-induced, and cytokine-induced senescence (PMID:25220407, PMID:25982278). Loss of ANT2 elevates reactive oxygen species and activates the DNA damage response, linking its downregulation mechanistically to the senescent phenotype (PMID:25220407). Post-translationally, ANT2 is integrated into a PAK6–SIRT4–ANT2 complex in which PAK6 phosphorylates ANT2 at T107 to inhibit apoptosis while SIRT4 deacetylates K105 to drive ubiquitin-mediated degradation, coordinately controlling ANT2 stability and pro-tumorigenic function (PMID:32194820). Beyond bioenergetics, genetic deletion studies show ANT2 controls mitochondrial permeability transition and ROS-driven inflammation: it sets adipocyte oxygen demand to cause obesity-associated hypoxia and HIF-1α induction (PMID:31528845), and mediates free fatty acid-induced permeability transition, ROS, HIF-1α and NF-κB activation to drive proinflammatory macrophage activation (PMID:34676827). Ant2 is also required cell-autonomously for erythroid and B-lymphocyte maturation (PMID:25613378). Independent of nucleotide transport, ANT2 functions as an RNA translocon that exports mitochondrial double-stranded RNA to the cytosol to trigger innate immune signaling (PMID:38811766). Microdeletions at Xq24 encompassing SLC25A5 are associated with non-syndromic intellectual disability in males (PMID:23783460).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    Established how ANT2 transcription is set, showing Sp1 functions as both activator and repressor of the proximal promoter through distinct GC-box elements.

    Evidence Promoter deletion/mutation reporter constructs, gel-shift and anti-Sp1 supershift assays across multiple cell lines

    PMID:8702555

    Open questions at the time
    • Does not explain how dual Sp1 function is biased toward activation versus repression in specific cell states
    • No link to physiological ANT2 protein levels established
  2. 1998 Medium

    Identified an additional repressive promoter motif (GRBOX) recognized by a negative regulator, refining the picture of ANT2 transcriptional silencing in proliferative cells.

    Evidence Promoter-deletion transfection and mobility gel-shift assays, yeast complementation

    PMID:9698557

    Open questions at the time
    • GRBOX-binding factor not identified
    • No in vivo confirmation of repression
  3. 1999 Medium

    Linked ANT2 gene regulation to chromosome architecture and to growth-cycle control, showing X-inactivation status and serum/confluence state govern transcription.

    Evidence Three-color FISH with 3D confocal imaging (X-territory positioning); actinomycin D block and promoter-deletion transfection during cell-cycle transitions

    PMID:10222150 PMID:10527626

    Open questions at the time
    • Causal relationship between 3D position and transcription not established
    • Identity of the confluence-responsive suppressor region factor unknown
  4. 2001 Medium

    Mechanistically dissected Sp1 repression, showing it depends on the Sp1 D transactivation domain and on inter-element positioning rather than steric occlusion.

    Evidence Sp1 deletion-mutant transfection in Drosophila SL2 and mammalian cells with promoter mutation analysis

    PMID:11683873

    Open questions at the time
    • Structural basis of Sp1-Sp1 interaction across elements not resolved
    • Not validated at the endogenous locus
  5. 2005 Medium

    Defined ANT2 directionality and disease context, showing it is induced in transformed and rho(0) cells and imports glycolytic ATP to sustain mitochondrial integrity.

    Evidence Cell-line expression analysis, yeast functional complementation under anaerobic conditions, hypoxia cell-cycle and metabolic profiling

    PMID:15486956 PMID:16341775

    Open questions at the time
    • Direct biochemical measurement of import-versus-export flux in human mitochondria not shown
    • Correlative cell-line comparisons without direct ANT2 manipulation in the hypoxia study
  6. 2010 Medium

    Connected ANT2 to oncogenic receptor signaling, showing its knockdown destabilizes HER2/neu and suppresses PI3K/Akt-driven invasion.

    Evidence shRNA knockdown, HER2-HSP90 Co-IP, PI3K/Akt and MMP activity and invasion assays in breast cancer cells

    PMID:20650008

    Open questions at the time
    • Whether the effect requires ANT2 transport activity not tested
    • Direct versus indirect link between ANT2 and HER2-HSP90 dissociation unresolved
  7. 2012 Medium

    Placed ANT2 in a non-bioenergetic complex, showing it associates with MMS19 and Fe-S apoproteins within the late cytosolic iron-sulfur assembly (CIA) complex.

    Evidence Co-immunoprecipitation mapping interactions within the CIA complex

    PMID:23150669

    Open questions at the time
    • Functional contribution of ANT2 to Fe-S cluster maturation not demonstrated
    • Single-lab Co-IP without reconstitution
  8. 2015 High

    Established ANT2 as a node in cellular senescence, showing TGF-β/NF1/Smad4 and IFNγ/JAK-STAT signaling repress ANT2, raising ROS and DNA damage.

    Evidence siRNA knockdown, ROS/DDR readouts, promoter binding assays for NF1/Smad complexes, pathway inhibitors across multiple senescence models; in vivo lineage requirement shown via Ant2 hypomorphic mice

    PMID:25220407 PMID:25613378 PMID:25982278

    Open questions at the time
    • Whether ANT2 loss drives senescence causally or is a marker not fully separated
    • Mechanism linking reduced ATP import to specific erythroid/B-cell maturation arrest incompletely defined
  9. 2018 High

    Demonstrated ANT2's organismal metabolic role and a therapeutic vulnerability, showing it drives adipocyte oxygen demand/hypoxia and that low ANT2 sensitizes senescent cells to MitoTam.

    Evidence Adipocyte-specific Ant2 knockout mice with O2/HIF-1α and metabolic phenotyping; ANT2 gain/loss in senescent vs non-senescent cells with in vivo MitoTam treatment

    PMID:29786070 PMID:31528845

    Open questions at the time
    • Molecular trigger coupling ANT2 transport to O2 consumption not fully defined
    • How ANT2 level dictates MitoTam sensitivity mechanistically unclear
  10. 2020 High

    Defined post-translational control of ANT2, showing a PAK6-SIRT4-ANT2 complex couples T107 phosphorylation and K105 deacetylation to control stability and apoptosis.

    Evidence Co-IP, immunoEM, site-directed mutagenesis (T107, K105), ubiquitination and apoptosis assays, xenografts; plus MFN2-loss hypoxia model showing ANT2 ATP import

    PMID:32194820 PMID:33255741

    Open questions at the time
    • Structural impact of T107/K105 modifications on transport not resolved
    • Generality of the PAK6-SIRT4 axis beyond prostate cancer untested
  11. 2021 High

    Extended ANT2's inflammatory role to macrophages, showing it mediates FFA-induced permeability transition, ROS, HIF-1α and NF-κB to drive obesity inflammation.

    Evidence Myeloid-specific ANT2-KO mice, permeability transition and ROS assays, HIF-1α/NF-κB analysis, metabolic phenotyping

    PMID:34676827

    Open questions at the time
    • Whether permeability transition role requires nucleotide transport function not isolated
    • Direct sensing mechanism for free fatty acids not defined
  12. 2022 Medium

    Revealed context-dependent and pharmacological dimensions of ANT2, spanning pro-adipogenic ERK signaling, tumor-suppressive behavior in colon cancer, and a druggable target in neuroblastoma.

    Evidence siRNA knockdown with RNA-seq/lipidomics and ERK inhibitor in OP9 cells; colon cancer cell functional/bioinformatic analysis; PENAO inhibition with SAHA combination in neuroblastoma lines and xenografts; chemical bead pulldown linking ANT2 to cyclin D1 control

    PMID:28368390 PMID:35109789 PMID:35288533 PMID:36346110

    Open questions at the time
    • Opposing oncogenic versus tumor-suppressive roles across tissues not reconciled mechanistically
    • Specificity of PENAO/ligand binding to ANT2 versus paralogs not fully resolved
  13. 2022 Medium

    Showed ANT2 gain-of-function reverses senescence-associated decline, accelerating wound healing via glycolytic ATP, mitophagy and HSPA6-mediated anti-inflammation.

    Evidence ANT2 overexpression in aged mouse skin wound model and in senescent human fibroblasts with ATP, mitophagy and HSPA6/inflammation readouts

    PMID:37211200

    Open questions at the time
    • Direct link between ANT2 transport and HSPA6 induction not established
    • Single-lab gain-of-function without loss-of-function rescue
  14. 2024 High

    Uncovered a transport function distinct from bioenergetics, showing ANT2 acts as an RNA translocon exporting mitochondrial dsRNA to trigger innate immunity.

    Evidence Direct RNA transport assays, mutagenesis separating RNA transport from ADP/ATP translocase activity, in vivo inflammation model

    PMID:38811766

    Open questions at the time
    • Structural basis distinguishing nucleotide versus RNA conduction unknown
    • Regulation of the switch between metabolic and RNA-export functions undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single carrier integrates nucleotide transport, RNA export, permeability-transition control, and post-translational regulation into context-specific outcomes (tumor-promoting versus tumor-suppressive, pro- versus anti-inflammatory) remains unresolved.
  • No unified structural model linking the distinct transport modes
  • Tissue-specific determinants of opposing phenotypes not defined
  • Whether senescence-associated repression is cause or consequence not settled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140104 molecular carrier activity 2 GO:0003723 RNA binding 1
Localization
GO:0005739 mitochondrion 4
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
C2ORF18HSP90MMS19PAK6SIRT4SP1
Complex memberships
PAK6-SIRT4-ANT2 complexcytosolic iron-sulfur cluster assembly (CIA) complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 ANT2 (SLC25A5) and ANT3 genes show differential 3D positioning within active versus inactive X chromosome territories in female human amniotic fluid cell nuclei: transcriptionally active ANT2 on the active X chromosome is positioned more peripherally within its chromosome territory, while the inactive ANT2 gene on the inactive X is positioned significantly more interior. ANT3, which escapes X-inactivation, is also positioned more peripherally. Three-color fluorescence in situ hybridization (FISH), confocal laser scanning microscopy, 3D image analysis Experimental cell research Medium 10527626
2005 ANT2 (SLC25A5) expression is specifically induced in transformed, tumoral, and mtDNA-lacking rho(0) cell lines relative to differentiated cells, and its expression correlates with glycolytic ATP production. A functional complementation assay in Saccharomyces cerevisiae demonstrated that human ANT2 specifically restores yeast cell growth under anaerobic conditions, consistent with its role in importing glycolytic ATP into mitochondria rather than exporting mitochondrial ATP. Cell line expression analysis, functional complementation in yeast, mitochondrial membrane potential inhibitor studies Journal of bioenergetics and biomembranes Medium 16341775
1998 The ANT2 (SLC25A5) proximal promoter contains a novel motif termed GRBOX that is recognized by a negative transcriptional regulator. Promoter-deletion transfection and mobility gel-shift assays revealed this motif is involved in repressing ANT2 expression, likely controlling the selective import of glycolytic ATP into mitochondria in highly proliferative cells. Promoter-deletion transfection assays, mobility gel-shift assays, functional complementation in yeast Journal of molecular biology Medium 9698557
1996 The ANT2 (SLC25A5) proximal promoter is regulated by Sp1 acting through three GC-box elements: two activating elements (A and B boxes) at distal positions that act synergistically, and one inhibitory element (C box, nucleotides -7 to -2) adjacent to the transcription start site. Sp1 bound to the C box decreases transcription initiation; mutations in C box increased reporter expression and inhibited Sp1 binding. This dual activator/repressor function of Sp1 is preserved across multiple cell lines. Transient transfection with promoter-deletion/mutation constructs, gel-shift assays, supershift experiments with anti-Sp1 antibodies The Journal of biological chemistry High 8702555
1999 ANT2 (SLC25A5) gene expression is regulated at the transcriptional level during growth activation. Actinomycin D completely blocked serum-induced ANT2 expression; no changes in transcript stability were observed during serum-induced G0-to-G1 transition or re-entry into G0. A suppressor region in the ANT2 promoter is responsible for decreased expression when cells approach confluence and exit the growth cycle. Actinomycin D block experiments, transcript stability assays, permanent transfection with promoter deletion constructs Experimental cell research Medium 10222150
2001 Sp1-mediated repression of the ANT2 (SLC25A5) promoter through the C-box element requires the D transactivation domain of Sp1 and depends on precise positioning of Sp1 at the C box relative to the A/B boxes. Repression is not due to steric interference with transcription machinery assembly. Separation of the A box and B box eliminates C-box-mediated repression, indicating Sp1 complexes on separate GC elements interact to repress activating Sp1 species. Transfection of Sp1 deletion mutants in Drosophila SL2 and mammalian cell lines, promoter mutation analysis European journal of biochemistry Medium 11683873
2005 ANT2 (SLC25A5) expression level in transformed cell lines correlates with maintenance of mitochondrial integrity and cell-cycle behavior under hypoxia. Cells with constitutive glycolytic activity and ANT2 overexpression (143B) continued proliferating under hypoxia, whereas cells with lower ANT2 expression (HepG2) arrested at G1/S. ATP import by ANT2 allows cells to maintain mitochondrial integrity independent of oxidative phosphorylation. Cell cycle analysis, metabolic profiling, comparison of ANT2 expression in cell lines with different metabolic backgrounds and their rho(0) derivatives Molecular carcinogenesis Low 15486956
2012 ANT2 (SLC25A5) interacts with Fe-S apoproteins and MMS19 within the cytosolic iron-sulfur cluster assembly (CIA) complex, but does not interact with individual CIA proteins (CIAO1 or Fe-S proteins alone). This places ANT2 in the late CIA complex as a component involved in cytoplasmic Fe-S cluster protein assembly. Co-immunoprecipitation, identification of protein interactions in the CIA complex The Journal of biological chemistry Medium 23150669
2015 ANT2 (SLC25A5) expression is consistently downregulated in all three major forms of cellular senescence (replicative, oncogene-induced, and drug-induced) in both normal and cancerous human cells. TGF-β signaling induces formation of NF1/Smad4 transcription repressor complexes that bind NF1-dependent repressor elements in the ANT2 promoter to suppress ANT2 expression. siRNA-mediated knockdown of ANT2 in proliferating cells increases reactive oxygen species (ROS) and activates the DNA damage response (DDR). siRNA knockdown, ROS measurement, DDR signaling analysis, promoter binding assays for NF1/Smad complexes, multiple senescence models Cellular signalling High 25220407
2015 IFNγ suppresses ANT2 (SLC25A5) expression through TGFβ/SMAD signaling, contributing to elevation of ROS and DNA damage. This suppression of ANT2 contributes to cytokine-induced cellular senescence. ANT2 suppression is downstream of JAK/STAT → TGFβ → Smad pathway activation by IFNγ. siRNA knockdown, ROS measurement, pathway inhibitor studies, senescence assays in human and mouse normal and cancer cell models Oncogene Medium 25982278
2018 Increased adipocyte O2 demand mediated by ANT2 (SLC25A5) activity is the dominant cause of adipocyte hypoxia in obesity. Adipocyte-specific deletion of Ant2 in mice reduces obesity-induced intracellular adipocyte hypoxia by decreasing O2 demand without affecting mitochondrial number/mass or oligomycin-sensitive respiration. This leads to decreased adipose tissue HIF-1α expression and inflammation, and improves glucose tolerance and insulin resistance. Adipocyte-specific Ant2 knockout mice, O2 tension measurements, HIF-1α expression analysis, metabolic phenotyping Nature metabolism High 31528845
2018 Susceptibility of senescent cells to mitochondria-targeted tamoxifen (MitoTam) is linked to very low ANT2 (SLC25A5) expression inherent to the senescent phenotype. Restoration of ANT2 in senescent cells conferred resistance to MitoTam, while downregulation of ANT2 in non-senescent cells promoted their MitoTam-triggered elimination. ANT2 overexpression and knockdown in senescent vs. non-senescent cells, cell viability assays, in vivo aging mouse model with MitoTam treatment Cell death and differentiation Medium 29786070
2015 Mitochondrial ATP transporter Ant2 (Slc25a5) depletion in mice causes macrocytic anemia and B lymphocytopenia through cell-autonomous maturation arrest of erythroid precursors and B lymphocyte developmental defects, associated with increased ROS and premature cell death. Splenocytes show reduced maximal respiration capacity, decreased cellular ATP levels, and increased mitochondrial permeability transition pore opening. Myeloid, megakaryocyte, and T-lymphocyte lineages are unaffected. Ant2 hypomorphic mice (targeted gene disruption), flow cytometry, ROS measurement, ATP level measurement, mitochondrial permeability transition pore assays Cell death and differentiation High 25613378
2020 ANT2 (SLC25A5) is part of a PAK6-SIRT4-ANT2 complex at the mitochondrial inner membrane. PAK6 directly phosphorylates ANT2 at T107 to inhibit apoptosis in prostate cancer cells. SIRT4 deacetylates ANT2 at K105 to promote its ubiquitination and degradation. PAK6 promotes SIRT4 ubiquitin-mediated proteolysis, thereby adjusting ANT2 acetylation level and stability. Phosphorylation and deacetylation of ANT2 are mutually regulated and together promote tumor growth. Co-immunoprecipitation, immunofluorescence, immunoelectron microscopy, ubiquitination assays, site-directed mutagenesis (T107, K105), flow cytometry, xenograft models Theranostics High 32194820
2017 ANT2 (SLC25A5) directly binds sesaminol (identified by sesaminol-immobilized FG bead pulldown). ANT2 depletion reduces cyclin D1 expression by decreasing its mRNA levels, inhibiting mTORC1 signaling, and promoting proteasomal degradation of cyclin D1 protein, mirroring the effects of sesaminol treatment. Troglitazone (a PPARγ agonist) also binds ANT2 and similarly reduces cyclin D1 expression. Ligand-immobilized FG bead pulldown, ANT2 siRNA depletion, cyclin D1 mRNA/protein analysis, mTORC1 activity assays, proteasome inhibitor experiments Oncogenesis Medium 28368390
2010 ANT2 (SLC25A5) shRNA knockdown decreases HER2/neu protein levels by promoting HER2/neu degradation through dissociation from HSP90. This inhibits the PI3K/Akt signaling pathway, leading to downregulation of MT1-MMP and VEGF, decreased MMP2/MMP9 activity, and suppression of breast cancer cell migration and invasion. ANT2 shRNA knockdown, co-immunoprecipitation of HER2-HSP90 complex, PI3K/Akt pathway analysis, MMP activity assays, migration/invasion assays BMC cancer Medium 20650008
2021 ANT2 (SLC25A5) mediates proinflammatory activation of adipose tissue macrophages in obesity. Ant2 expression is increased in adipose tissue macrophages (ATMs) of obese mice. Myeloid-specific ANT2-knockout mice show decreased adipose tissue inflammation and improved insulin sensitivity. Mechanistically, ANT2 mediates free fatty acid-induced mitochondrial permeability transition, leading to increased mitochondrial ROS production and damage, which increases HIF-1α expression and NF-κB activation to drive proinflammatory macrophage activation. Myeloid-specific ANT2-KO mice, mitochondrial permeability transition assays, ROS measurement, HIF-1α and NF-κB activation analysis, metabolic phenotyping JCI insight High 34676827
2022 Slc25a5 (ANT2) knockdown in OP9 adipogenic cells suppresses adipogenic differentiation, reduces triglyceride accumulation, inhibits PPARγ protein expression, and decreases oxidative phosphorylation protein expression and ATP production. The pro-adipogenic effect of Slc25a5 is mediated through ERK1/2 phosphorylation, as confirmed by the ERK1/2 inhibitor PD98059 phenocopying knockdown effects. siRNA knockdown, RNA-seq, lipidomics, Oil Red O staining, OXPHOS protein expression, ATP measurement, ERK inhibitor treatment Cellular & molecular biology letters Medium 35109789
2008 C2orf18 (ANT2BP, ANT2-binding protein) localizes to mitochondria and directly interacts with ANT2 (SLC25A5), suggesting ANT2 participates in a complex involved in maintenance of mitochondrial membrane potential and energy homeostasis in pancreatic cancer cells. Co-immunoprecipitation, subcellular localization studies, siRNA knockdown of C2orf18 Cancer science Low 19154410
2020 During hypoxia, ANT2 (SLC25A5) protein is overexpressed following MFN2 loss-of-function and imports cytosolic ATP into mitochondria to maintain mitochondrial ATP concentration and inner membrane potential. This ANT2-mediated ATP import, in concert with decreased ATP hydrolase activity via IF1, blunts detrimental hyperpolarization of the inner mitochondrial membrane upon re-oxygenation and reduces cardiomyocyte cell death. MFN2 knockdown, ATP and membrane potential measurements, ANT2 protein expression analysis in hypoxia-reoxygenation model Cells Medium 33255741
2022 High SLC25A5 expression in colon cancer cell lines attenuates cell proliferation, upregulates programmed cell death-related signatures, and inhibits the MAPK signaling pathway. SLC25A5 was found to be downregulated in colon cancer compared to normal tissue. Functional experiments in colon cancer cell lines, bioinformatic analysis, immunohistochemistry Cell death & disease Low 35288533
2013 Microdeletions at Xq24 encompassing SLC25A5 but not SLC25A43 are associated with non-syndromic intellectual disability in males, pointing to SLC25A5 as a novel gene for non-syndromic ID. An intragenic deletion of SLC25A43 alone in a healthy boy excluded SLC25A43 as the causative gene, leaving SLC25A5 as the candidate. SLC25A5 is highly expressed in cortex and hippocampus and is presumed to function in mitochondrial ADP/ATP exchange. Microdeletion mapping by junction sequencing, expression analysis in brain regions, genetic exclusion of SLC25A43 Human genetics Low 23783460
2022 ANT2 (SLC25A5) overexpression in aged mouse skin accelerates wound healing of full-thickness cutaneous wounds. In replicative senescent human dermal fibroblasts, ANT2 overexpression induces cell proliferation and migration, increases ATP production by activating glycolysis, induces mitophagy, and upregulates HSPA6, which downregulates proinflammatory genes mediating cellular senescence and mitochondrial damage. ANT2 overexpression in aged mouse skin (in vivo wound healing model), ANT2 overexpression in senescent human fibroblasts, ATP production assays, mitophagy assays, HSPA6 expression analysis The Journal of investigative dermatology Medium 37211200
2024 ANT2 (SLC25A5) functions as an RNA translocon in the mitochondrial inner membrane, mediating bidirectional cross-membrane transport of RNAs including mitochondrial double-stranded RNA (dsRNA), independent of its ADP/ATP translocase activity. ANT2-mediated dsRNA efflux to the cytosol triggers innate immune signaling. Inhibiting ANT2-dependent dsRNA export alleviates inflammation in vivo. Direct mechanistic evidence for RNA transport through ANT2, separation of RNA transport from ADP/ATP translocase function by mutagenesis/functional assays, in vivo inflammation model Cell research High 38811766
2022 Inhibiting SLC25A5/ANT2 with PENAO reduces cell viability in neuroblastoma cell lines in a TP53-status-dependent manner. Combined treatment of PENAO with SAHA (a histone deacetylase inhibitor) synergistically reduces cell viability and induces apoptosis independent of TP53 status, and significantly delays tumor progression in pre-clinical neuroblastoma mouse models. SLC25A5 inhibition by PENAO in a panel of neuroblastoma cell lines, drug combination viability assays, apoptosis assays, xenograft mouse models International journal of cancer Medium 36346110

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1975 Opposite effects of dexamethasone on serum concentrations of 3,3',5'-triiodothyronine (reverse T3) and 3,3'5-triiodothyronine (T3). The Journal of clinical endocrinology and metabolism 343 1242390
1987 Yeast mitochondrial RNA polymerase is homologous to those encoded by bacteriophages T3 and T7. Cell 341 3308116
1997 Substrate specificities of three members of the human UDP-N-acetyl-alpha-D-galactosamine:Polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3. The Journal of biological chemistry 253 9295285
1996 Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors. Molecular endocrinology (Baltimore, Md.) 210 8813722
1987 Endocytosis and recycling of the T3-T cell receptor complex. The role of T3 phosphorylation. The Journal of experimental medicine 200 3104527
1997 Signal transduction mediated by the truncated trkB receptor isoforms, trkB.T1 and trkB.T2. The Journal of neuroscience : the official journal of the Society for Neuroscience 196 9092589
2005 Cardiac iron determines cardiac T2*, T2, and T1 in the gerbil model of iron cardiomyopathy. Circulation 182 16027257
1992 Triiodothyronine (T3) decreases binding to DNA by T3-receptor homodimers but not receptor-auxiliary protein heterodimers. The Journal of biological chemistry 174 1740410
2019 TLR8 Is a Sensor of RNase T2 Degradation Products. Cell 163 31778653
2008 Thyroid hormone (T3) and TRbeta agonist GC-1 inhibit/reverse nonalcoholic fatty liver in rats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 128 18434432
2014 Thyroid hormones, t3 and t4, in the brain. Frontiers in endocrinology 126 24744751
2019 A Transcriptomic Method to Determine Airway Immune Dysfunction in T2-High and T2-Low Asthma. American journal of respiratory and critical care medicine 125 30371106
2020 T2-"Low" Asthma: Overview and Management Strategies. The journal of allergy and clinical immunology. In practice 124 32037109
2013 Coordination of hypothalamic and pituitary T3 production regulates TSH expression. The Journal of clinical investigation 119 23524969
1976 SAMase gene of bacteriophage T3 is responsible for overcoming host restriction. Journal of virology 116 781304
2002 Ribonucleases from T2 family. Critical reviews in microbiology 105 12109772
2014 Defending plasma T3 is a biological priority. Clinical endocrinology 104 25040645
2005 ANT2 isoform required for cancer cell glycolysis. Journal of bioenergetics and biomembranes 101 16341775
1999 The 3D positioning of ANT2 and ANT3 genes within female X chromosome territories correlates with gene activity. Experimental cell research 101 10527626
1998 Expression of human ANT2 gene in highly proliferative cells: GRBOX, a new transcriptional element, is involved in the regulation of glycolytic ATP import into mitochondria. Journal of molecular biology 96 9698557
2018 Knockdown of Ant2 Reduces Adipocyte Hypoxia And Improves Insulin Resistance in Obesity. Nature metabolism 94 31528845
1992 Triiodothyronine (T3) differentially affects T3-receptor/retinoic acid receptor and T3-receptor/retinoid X receptor heterodimer binding to DNA. The Journal of biological chemistry 93 1331079
1985 The T3/T cell receptor complex: antigenic distinction between the two 20-kd T3 (T3-delta and T3-epsilon) subunits. The EMBO journal 85 2410254
2018 Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2. Cell death and differentiation 82 29786070
2015 IFNγ induces oxidative stress, DNA damage and tumor cell senescence via TGFβ/SMAD signaling-dependent induction of Nox4 and suppression of ANT2. Oncogene 80 25982278
1993 DNA packaging ATPase of bacteriophage T3. Virology 79 8460483
1985 Sequence and analysis of the gene for bacteriophage T3 RNA polymerase. Nucleic acids research 78 3903658
2004 Recurrent advanced (T3 or T4) head and neck squamous cell carcinoma: is salvage possible? Archives of otolaryngology--head & neck surgery 74 14732765
1995 Radiotherapy for T2 and T3 carcinoma of the bladder: the influence of overall treatment time. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 72 8532904
1996 Sp1 activates and inhibits transcription from separate elements in the proximal promoter of the human adenine nucleotide translocase 2 (ANT2) gene. The Journal of biological chemistry 70 8702555
1991 Oligomeric binding of T3 receptor is required for maximal T3 response. The Journal of biological chemistry 69 1918070
2007 Thyroid hormone (T3) rapidly activates p38 and AMPK in skeletal muscle in vivo. Journal of applied physiology (Bethesda, Md. : 1985) 61 17962579
1986 Triiodothyronine (T3) regulation of thyrotropin subunit gene transcription is proportional to T3 nuclear receptor occupancy. Endocrinology 61 2416554
2022 Generation and Comparative Analysis of an Itga8-CreER Mouse with Preferential Activity in Vascular Smooth Muscle Cells. Nature cardiovascular research 59 36424917
1995 Segregation analysis of four translocations, t(2;18), t(3;15), t(5;7), and t(10;12), by sperm chromosome studies and a review of the literature. Cytogenetics and cell genetics 59 7736796
2017 Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms. International journal of molecular sciences 57 28362337
1999 The growth-dependent expression of the adenine nucleotide translocase-2 (ANT2) gene is regulated at the level of transcription and is a marker of cell proliferation. Experimental cell research 52 10222150
2008 Hepatic regulation of fatty acid synthase by insulin and T3: evidence for T3 genomic and nongenomic actions. American journal of physiology. Endocrinology and metabolism 51 18682535
1999 Differential expression of trkB.T1 and trkB.T2, truncated trkC, and p75(NGFR) in the cochlea prior to hearing function. The Journal of comparative neurology 49 10494076
2020 Mitochondrial PAK6 inhibits prostate cancer cell apoptosis via the PAK6-SIRT4-ANT2 complex. Theranostics 48 32194820
2016 Vegfr3-CreER (T2) mouse, a new genetic tool for targeting the lymphatic system. Angiogenesis 48 26993803
2017 Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma. Oncology reports 47 28350139
2009 Cyclin T2 is essential for mouse embryogenesis. Molecular and cellular biology 44 19364821
2009 Overexpression of the mitochondrial T3 receptor induces skeletal muscle atrophy during aging. PloS one 44 19462004
2005 ANT2 expression under hypoxic conditions produces opposite cell-cycle behavior in 143B and HepG2 cancer cells. Molecular carcinogenesis 44 15486956
2015 Mitochondrial ATP transporter Ant2 depletion impairs erythropoiesis and B lymphopoiesis. Cell death and differentiation 43 25613378
2014 TGF-β/NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence. Cellular signalling 43 25220407
2022 Triiodothyronine (T3) promotes brown fat hyperplasia via thyroid hormone receptor α mediated adipocyte progenitor cell proliferation. Nature communications 42 35697700
2016 ANT2 shRNA downregulates miR-19a and miR-96 through the PI3K/Akt pathway and suppresses tumor growth in hepatocellular carcinoma cells. Experimental & molecular medicine 42 27012708
1998 The t(2;5) in human lymphomas. Leukemia & lymphoma 41 9684923
2022 An integrated bioinformatic investigation of mitochondrial solute carrier family 25 (SLC25) in colon cancer followed by preliminary validation of member 5 (SLC25A5) in tumorigenesis. Cell death & disease 40 35288533
2011 Thyroid hormone T3 counteracts STZ induced diabetes in mouse. PloS one 40 21637761
2012 The mammalian proteins MMS19, MIP18, and ANT2 are involved in cytoplasmic iron-sulfur cluster protein assembly. The Journal of biological chemistry 39 23150669
2008 Triiodothyronine (T3) stimulates food intake via enhanced hypothalamic AMP-activated kinase activity. Regulatory peptides 38 18708095
2013 ANT2 suppression by shRNA restores miR-636 expression, thereby downregulating Ras and inhibiting tumorigenesis of hepatocellular carcinoma. Experimental & molecular medicine 36 23306701
1993 Promoter independent down-regulation of the firefly luciferase gene by T3 and T3 receptor in CV1 cells. Molecular and cellular endocrinology 36 8243799
1977 Isolation of recombinants between T7 and T3 bacteriophages and their use in vitro transcriptional mapping. Journal of virology 36 833947
2014 Degradation of acetochlor by a bacterial consortium of Rhodococcus sp.T3-1, Delftia sp.T3-6 and Sphingobium sp.MEA3-1. Letters in applied microbiology 34 24605783
1994 Ligand (T3) dependent and independent effects of thyroid hormone receptors upon human TRH gene transcription in neuroblastoma cells. Biochemical and biophysical research communications 33 8166684
2010 Degradation of HER2/neu by ANT2 shRNA suppresses migration and invasiveness of breast cancer cells. BMC cancer 32 20650008
1988 Head structure of bacteriophages T2 and T4. Journal of ultrastructure and molecular structure research 31 3198952
1980 T4, T3 and reverse T3 in the plasma of rats during the first 3 months of life. Acta endocrinologica 31 7386115
2022 Slc25a5 regulates adipogenesis by modulating ERK signaling in OP9 cells. Cellular & molecular biology letters 30 35109789
2018 FLOWERING LOCUS T3 Controls Spikelet Initiation But Not Floral Development. Plant physiology 30 30213796
2017 The pleiotropic regulation of cyclin D1 by newly identified sesaminol-binding protein ANT2. Oncogenesis 30 28368390
2013 AMPK signaling pathway is rapidly activated by T3 and regulates the cardiomyocyte growth. Molecular and cellular endocrinology 30 23748029
2019 Mutation update on ACAT1 variants associated with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. Human mutation 29 31268215
2018 Targeted knock-in of CreER T2 in zebrafish using CRISPR/Cas9. Cell and tissue research 29 29435650
2017 T2 Magnetic Resonance for Fungal Diagnosis. Methods in molecular biology (Clifton, N.J.) 29 27837513
2014 3,5-Diiodothyronine (T2) is on a role. A new hormone in search of recognition. General and comparative endocrinology 29 24602963
2016 Targeting Adenine Nucleotide Translocase-2 (ANT2) to Overcome Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Non-Small Cell Lung Cancer. Molecular cancer therapeutics 28 26883272
1990 Synthesis of functional mRNA in mammalian cells by bacteriophage T3 RNA polymerase. Molecular and cellular biology 28 2167433
2021 ANT2 drives proinflammatory macrophage activation in obesity. JCI insight 26 34676827
2013 The mitochondrial solute carrier SLC25A5 at Xq24 is a novel candidate gene for non-syndromic intellectual disability. Human genetics 25 23783460
1998 Tumour volume: implications in T2/T3 glottic/supraglottic squamous cell carcinoma. The Journal of otolaryngology 25 9800621
1990 T3 receptor occupancy and T3 levels in plasma and cytosol during rat brain development. Acta endocrinologica 25 2389629
2017 Mitochondrial T3 receptor and targets. Molecular and cellular endocrinology 24 28167126
2001 Sp1 acts as a repressor of the human adenine nucleotide translocase-2 (ANT2) promoter. European journal of biochemistry 22 11683873
1986 Triiodothyronine (T3)-induced down-regulation of the nuclear T3 receptor in mouse preadipocyte cell lines. Endocrinology 22 3769873
1989 T2/T3 bladder carcinomas treated with definitive radiotherapy with emphasis on flow cytometric DNA ploidy values. International journal of radiation oncology, biology, physics 21 2808053
1976 Binding of nuclear triiodothyronine (T3) binding protein-T3 complex to chromatin. Endocrinology 20 11991
2022 Inhibition of mitochondrial translocase SLC25A5 and histone deacetylation is an effective combination therapy in neuroblastoma. International journal of cancer 19 36346110
2020 Clinical and laboratory aspects of 3,3',5'-triiodothyronine (reverse T3). Annals of clinical biochemistry 19 33040575
2011 Thyroid hormones (T3 and T4): dual effect on human cancer cell proliferation. Anticancer research 19 21273585
1997 The rapidly evolving Pem homeobox gene and Agtr2, Ant2, and Lamp2 are closely linked in the proximal region of the mouse X chromosome. Genomics 19 9344676
2015 Differential infiltration of neutrophils in T1-T2 versus T3-T4 oral squamous cell carcinomas: a preliminary study. BMC research notes 18 26467671
1988 Stable T3- and T3+ subclones derived from the mosaic human T cell leukemia cell line, CEM. Journal of immunology (Baltimore, Md. : 1950) 18 2895794
2015 Sox10ER(T2) CreER(T2) mice enable tracing of distinct neural crest cell populations. Developmental dynamics : an official publication of the American Association of Anatomists 17 26250625
2014 Regulatory feedback loop between T3 and microRNAs in renal cancer. Molecular and cellular endocrinology 17 24440748
1988 Packaging and transduction of non-T3 DNA by bacteriophage T3. Virology 17 2972112
1980 Mapping of promoter sites utilized by T3 RNA polymerase on T3 DNA. Nucleic acids research 17 7443532
2023 ANT2 Accelerates Cutaneous Wound Healing in Aged Skin by Regulating Energy Homeostasis and Inflammation. The Journal of investigative dermatology 16 37211200
2022 Robotic partial nephrectomy for management of renal mass in patients with a solitary kidney: can we expand the indication to T2 and T3 disease? Minerva urology and nephrology 16 35345388
2020 ANT2-Mediated ATP Import into Mitochondria Protects against Hypoxia Lethal Injury. Cells 16 33255741
2019 Investigations of Accessibility of T2/T3 Copper Center of Two-Domain Laccase from Streptomyces griseoflavus Ac-993. International journal of molecular sciences 16 31261802
2013 Genes that characterize T3-predominant Graves' thyroid tissues. European journal of endocrinology 16 23109646
2010 Inhibition of insulin and T3-induced fatty acid synthase by hexanoate. Lipids 16 20811782
2008 Identification of C2orf18, termed ANT2BP (ANT2-binding protein), as one of the key molecules involved in pancreatic carcinogenesis. Cancer science 16 19154410
2024 ANT2 functions as a translocon for mitochondrial cross-membrane translocation of RNAs. Cell research 15 38811766
2022 Specific Therapy for T2 Asthma. Journal of personalized medicine 15 35455709

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