Affinage

Showing SLC25A4 — ANT1 is a alias.

SLC25A4

ADP/ATP translocase 1 · UniProt P12235

Audit flag: ungrounded claim
Length
298 aa
Mass
33.1 kDa
Annotated
2026-06-10
90 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC25A4 (ANT1) is the heart/muscle isoform of the mitochondrial ADP/ATP carrier that exchanges matrix ATP for cytosolic ADP across the inner membrane, a function established directly by reconstitution and transport assays in which pathogenic mutants are impaired (PMID:27693233, PMID:21586654, PMID:30046662). Beyond nucleotide exchange, reconstitution of purified ANT1 in planar lipid bilayers shows it mediates H+ transport only in the presence of long-chain fatty acids, consistent with a fatty acid cycling mechanism in which FA anions slide along the positively charged protein-lipid interface and are protonated at R79, a residue that also governs ADP/ATP and inhibitor (carboxyatractyloside, bongkrekic acid) binding (PMID:33801254, PMID:37762012); this protonophoric activity is sensitive to membrane curvature elastic stress set by bilayer lipid composition (PMID:36552523), and ANT1 mediates fatty-acid-induced uncoupling in skeletal muscle and brown-fat mitochondria (PMID:16831128, PMID:26886198). ANT1 also confers voltage-sensitivity to the mitochondrial permeability transition pore, since cells lacking ANT1 resist Ca2+- and H2O2-induced swelling and show altered mPT voltage thresholds (PMID:27221760). Pathogenic missense mutations act dominantly: equivalent substitutions in yeast and Podospora impair ADP/ATP exchange, destabilize mtDNA as a dominant (gain-of-function) trait, and—for adPEO-type alleles—misfold and aggregate in the inner membrane, disrupting assembly of multiple membrane complexes (PMID:15016764, PMID:25833713, PMID:28947214, PMID:19687137), while complete loss of ANT1 in a patient causes cardiomyopathy/myopathy with mitochondrial proliferation and multiple mtDNA deletions (PMID:22187496). ANT1 is embedded in regulatory networks controlling its abundance and activity: its transcription is repressed by NF-κB and by the MeCP2/YY1 complex (PMID:28877317, PMID:20504995), it is dephosphorylated by mitochondrial SHP2 to limit NLRP3 inflammasome hyperactivation (PMID:29255148), denitrosylated at C160 by mitochondrial GSNOR to preserve membrane potential and mitophagy (PMID:37377022), and stabilized by USP34-mediated deubiquitination to support PINK1/Parkin mitophagy (PMID:41631201); ANT1 itself acts upstream of PINK1/Parkin recruitment (PMID:34986425). Restoring ~10% of Ant1 expression rescues murine cardiomyopathy, confirming dosage-sensitive control of cardiac mitochondrial gene programs (PMID:41398158).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1992 Medium

    Establishing the genomic locus of the muscle ADP/ATP translocator provided the foundation for linking ANT1 to human disease.

    Evidence Fluorescence in situ hybridization mapping ANT1 to chromosome 4q35

    PMID:1582253

    Open questions at the time
    • Mapping alone establishes no function or mechanism
    • No allelic disease association at this stage
  2. 2004 High

    Modeling adPEO-equivalent mutations in yeast first showed that pathogenic ANT1 alleles impair ADP/ATP exchange and destabilize mtDNA dominantly, distinguishing the disease mechanism from simple loss of function.

    Evidence Yeast AAC2 complementation with transport assays, cytochrome spectroscopy, and heteroallelic mtDNA stability tests

    PMID:15016764

    Open questions at the time
    • Yeast model does not directly establish the human residue-level transport defect
    • Does not resolve whether dominance arises from aggregation or altered transport
  3. 2004 Medium

    ANT1 overexpression was shown to trigger apoptosis by recruiting the IκBα–NF-κB complex to mitochondria in an isoform-specific manner, linking the carrier to cell-death signaling.

    Evidence Overexpression with subcellular fractionation, NF-κB EMSA, and p65 rescue; ANT2 negative control

    PMID:15231833

    Open questions at the time
    • Overexpression may not reflect endogenous behavior
    • Direct ANT1–IκBα binding not demonstrated
  4. 2006 Medium

    Pharmacological dissection of brown-fat versus liver mitochondria identified ANT1 as a contributor to basal proton leak, extending its role beyond nucleotide exchange.

    Evidence Carboxyatractyloside inhibition of respiration in isolated mitochondria with isoform-specific expression analysis

    PMID:16831128

    Open questions at the time
    • ANT1 role inferred indirectly from isoform expression pattern
    • Molecular basis of proton conductance not resolved here
  5. 2009 Medium

    Suppressor genetics in Podospora showed that mtDNA instability from ANT1 mutations is not solely caused by reduced membrane potential or ROS, separating these phenotypes.

    Evidence Fungal dominant mutation analysis with membrane potential, ROS, mtDNA deletion, and suppressor allele tests

    PMID:19687137

    Open questions at the time
    • Causal pathway from carrier dysfunction to mtDNA deletion remains undefined
    • Fungal model may not capture mammalian specifics
  6. 2010 Medium

    Two studies placed ANT1 abundance under physiological control—repression by MeCP2/YY1 and induction by PGC-1α—linking ANT1 dosage to neuronal (Rett) and cardiac ischemia phenotypes.

    Evidence MeCP2-YY1 Co-IP and promoter reporters in null cells/brain; PGC-1α overexpression with gene array and ANT1 siRNA rescue in cardiomyocytes

    PMID:20504995 PMID:20600099

    Open questions at the time
    • Direct transcription-factor occupancy of the endogenous locus in vivo not fully resolved for all factors
    • How ANT1 dosage mechanistically drives ischemia-reperfusion injury not defined
  7. 2011 High

    Expression of adPEO mutant ANT1 in mammalian myotubes demonstrated a dominant gain-of-function with abnormal reversal potential, refining the disease mechanism in disease-relevant cells.

    Evidence Mutant ANT1 in mouse myotubes with ADP-ATP exchange assay, electrophysiology, and siRNA controls

    PMID:21586654

    Open questions at the time
    • Does not address mtDNA instability mechanism
    • Aggregation contribution not assessed in this system
  8. 2011 Medium

    A human homozygous null established that complete ANT1 loss causes cardiomyopathy/myopathy with mtDNA deletions and no ANT3 compensation, defining the loss-of-function phenotype.

    Evidence Patient molecular diagnosis, RT-PCR, metabolic profiling, and muscle histology

    PMID:22187496

    Open questions at the time
    • Single case
    • Mechanism connecting null allele to mtDNA deletions not resolved
  9. 2015 Medium

    Yeast biochemistry revealed that adPEO mutations cause inner-membrane misfolding and aggregation that disrupt multiple membrane complexes, reframing these diseases as protein-misfolding disorders.

    Evidence Yeast Aac2 mutagenesis with native gels, pulse-chase, and aggregate microscopy

    PMID:25833713

    Open questions at the time
    • Aggregation demonstrated in yeast, not in human muscle
    • Relative contribution of misfolding versus transport defect to pathology unresolved
  10. 2016 High

    Direct transport reconstitution of patient mutants plus muscle biochemistry confirmed severe ADP/ATP transport impairment with mtDNA loss and respiratory deficiency.

    Evidence Recombinant R80H/R235G transport assays with orthogonal patient muscle analysis

    PMID:27693233

    Open questions at the time
    • Does not distinguish transport defect from misfolding contribution in vivo
    • Mechanism of dominance addressed separately
  11. 2016 Medium

    Loss-of-function cell models established ANT1 as the determinant conferring proton-gradient voltage sensitivity to the permeability transition pore.

    Evidence mPT swelling, calcium uptake, and voltage-threshold assays in ANT1-deficient fibroblasts and knockdown myotubes

    PMID:27221760

    Open questions at the time
    • Whether ANT1 is a structural pore component or a regulator not resolved
    • Single lab
  12. 2016 Medium

    ANT1 was shown to mediate fatty-acid-induced uncoupling in skeletal muscle with consequences for insulin-stimulated glucose uptake, tying its uncoupling activity to metabolism.

    Evidence siRNA knockdown in C2C12 myotubes and carboxyatractyloside inhibition in ZDF rat mitochondria with respiration and glucose-uptake assays

    PMID:26886198

    Open questions at the time
    • Molecular mechanism of proton transport not addressed here
    • In vivo physiological relevance not established
  13. 2017 High

    ANT1 was identified as a post-translational target of mitochondrial SHP2 that limits NLRP3 inflammasome hyperactivation, and as a transcriptional target repressed by NF-κB.

    Evidence SHP2-ANT1 Co-IP, macrophage SHP2 KO, and peritonitis model; NF-κB ChIP and promoter reporter with mitochondrial functional assays

    PMID:28877317 PMID:29255148

    Open questions at the time
    • SHP2 phosphosite on ANT1 not mapped
    • How dephosphorylation alters carrier activity unresolved
  14. 2018 Medium

    Yeast heteroallelic versus hemiallelic comparison demonstrated that de novo dominant ANT1 mutations are gain-of-function rather than haploinsufficient, and a separate L. lactis reconstitution defined loss of transport as the pathogenic mechanism for p.Lys33Gln.

    Evidence Yeast AAC2 genetic epistasis and L. lactis membrane-vesicle transport assay with patient muscle validation

    PMID:28947214 PMID:30046662

    Open questions at the time
    • Different alleles may act through different mechanisms
    • Single-case reconstitution studies
  15. 2018 Medium

    A brain-specific Ant1 conditional knockout linked ANT1 mitochondrial dysfunction to serotonergic neuronal dysregulation, expanding the phenotypic reach of ANT1 deficiency.

    Evidence Conditional heterozygous Ant1 KO mice with electrophysiology, serotonin turnover, and COX histochemistry

    PMID:29892051

    Open questions at the time
    • Mechanistic link from carrier loss to neuronal hyperexcitability undefined
    • Single lab
  16. 2021 High

    Bilayer reconstitution of purified ANT1 directly demonstrated fatty-acid-dependent H+ transport inhibited by nucleotides and ANT-specific inhibitors, establishing a fatty acid cycling mechanism.

    Evidence Planar lipid bilayer electrophysiology, FCS quantification, and molecular dynamics

    PMID:33801254

    Open questions at the time
    • Physiological role of this proton transport in vivo not established here
    • Stoichiometry of FA cycling not defined
  17. 2022 Medium

    ANT1 was placed upstream of the PINK1/Parkin mitophagy pathway, and its protonophoric activity shown to respond to membrane curvature elastic stress, connecting lipid biophysics to ANT1 function.

    Evidence BaP/BPDE exposure with ANT1 overexpression and PINK1/Parkin localization; bilayer electrophysiology with defined lipid compositions and MD lateral-pressure simulations

    PMID:34986425 PMID:36552523

    Open questions at the time
    • How ANT1 mechanistically promotes PINK1 OMM retention unresolved
    • Membrane-stress sensing not validated in intact mitochondria
  18. 2023 High

    Two studies defined residue-level mechanisms: R79 protonates sliding FA anions and governs nucleotide/inhibitor binding, while GSNOR-mediated denitrosylation at C160 preserves membrane potential and mitophagy in heart failure.

    Evidence Bilayer electrophysiology with site-directed mutagenesis and MD; biotin-switch/LC-MS/MS, C160A mutagenesis, cardiac GSNOR KO and AAV9 rescue

    PMID:37377022 PMID:37762012

    Open questions at the time
    • Interplay between R79 transport role and FA protonation not fully separated
    • Upstream control of mitochondrial GSNOR not defined
  19. 2025 Medium

    Gene therapy and post-translational stabilization studies established ANT1 dosage control: ~10% Ant1 restoration rescues murine cardiomyopathy, and USP34 deubiquitination stabilizes ANT1 to drive PINK1/Parkin mitophagy.

    Evidence AAV2/9 Ant1 delivery with proteomics and snRNA-seq; chondrocyte Usp34 KO mice with USP34-ANT1 Co-IP and ubiquitination assays

    PMID:41398158 PMID:41631201

    Open questions at the time
    • USP34 ubiquitination site on ANT1 not mapped
    • Threshold relationship between ANT1 dose and tissue rescue not generalized beyond heart

Open questions

Synthesis pass · forward-looking unresolved questions
  • How mutant ANT1 misfolding clogs the mitochondrial import machinery and how this is buffered remains to be resolved at the mechanistic level.
  • Preprint, not peer-reviewed
  • Import-clogging mechanism not demonstrated in mammalian cells
  • Relationship between import clogging and the established aggregation phenotype unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0008289 lipid binding 3 GO:0140104 molecular carrier activity 3 GO:0005198 structural molecule activity 1
Localization
GO:0005739 mitochondrion 5
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
GSNORIKBAMECP2NFKB1SHP2USP34YY1
Complex memberships
mitochondrial permeability transition pore

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 Recombinant AAC1 (SLC25A4) mutant proteins R80H and R235G are severely impaired in ADP/ATP transport in vitro, affecting substrate binding and mechanics of the carrier respectively, and cause marked loss of mtDNA copy number and respiratory chain deficiencies in skeletal muscle. Recombinant protein expression, ADP/ATP transport assay, patient muscle analysis (western blot, respiratory chain enzyme activities) American journal of human genetics High 27693233
2011 adPEO-associated mutant human ANT1 expressed in differentiated mouse myotubes causes dominant mitochondrial defects: decreased ADP-ATP exchange function and abnormal translocator reversal potential, with exchange reversal occurring at higher than normal membrane potential; these changes differ from simple ANT1 loss of function. Expression of mutant ANT1 in mouse myotubes; ADP-ATP exchange assay; electrophysiology measuring reversal potential; Ant1 siRNA knockdown as control Human molecular genetics High 21586654
2004 Yeast AAC2 mutations equivalent to human adPEO ANT1 mutations reduce ADP versus ATP transport and show a defect in ADP/ATP exchange ratio; in heteroallelic strains, reduced cytochrome content and increased mtDNA instability behave as dominant traits, demonstrating that pathogenic ANT1 mutations impair oxidative phosphorylation and destabilize mtDNA. Yeast complementation (Saccharomyces cerevisiae), ATP/ADP transport assay, cytochrome spectroscopy, cytochrome c oxidase activity, respiratory growth assay, mtDNA stability assay in heteroallelic strains Human molecular genetics High 15016764
2021 Purified recombinant ANT1 reconstituted in planar lipid bilayers mediates H+ transport only in the presence of long-chain fatty acids (not as a basal proton leak), dependent on fatty acid chain length and saturation; this transport is inhibited by purine nucleotides (preference ATP/ADP) and by the specific ANT1 inhibitors carboxyatractyloside and bongkrekic acid, consistent with a fatty acid cycling mechanism at the lipid-protein interface. Reconstitution of purified recombinant ANT1 in planar lipid bilayers; electrophysiology (membrane current measurement); fluorescence correlation spectroscopy for protein quantification; molecular dynamics simulation International journal of molecular sciences High 33801254
2023 ANT1 transports fatty acid anions back across the inner mitochondrial membrane via a 'FA sliding' mechanism: FA anions are attracted by positively charged arginines/lysines on the matrix side, slide along the positively charged protein-lipid interface, and bind to R79 where they are protonated. R79 is also critical for competitive binding of ADP/ATP substrates and the inhibitors carboxyatractyloside and bongkrekic acid. Planar lipid bilayer electrophysiology; site-directed mutagenesis of ANT1; molecular dynamics simulations International journal of molecular sciences High 37762012
2017 NLRP3 inflammasome stimulators trigger SHP2 translocation to mitochondria where it interacts with and dephosphorylates ANT1, preventing collapse of mitochondrial membrane potential and subsequent release of mitochondrial DNA and ROS, thereby limiting NLRP3 hyperactivation. Ablation or inhibition of SHP2 in macrophages intensifies NLRP3 activation. Co-immunoprecipitation of SHP2 and ANT1; mitochondrial fractionation; genetic ablation (SHP2 knockout macrophages); overexpression; cytokine measurement; peritonitis model Nature communications High 29255148
2023 Mitochondrial GSNOR denitrosylates ANT1 at cysteine 160 (C160). Under heart failure conditions, decreased mitochondrial GSNOR leads to elevated S-nitrosylation of ANT1 at C160, impairing mitochondrial membrane potential and mitophagy. Overexpression of non-nitrosylatable ANT1 C160A mutant or mitochondrial GSNOR improved mitochondrial function. Biotin-switch assay; LC-MS/MS identification of S-nitrosylation site (C160); cellular fractionation; immunofluorescence; cardiac-specific GSNOR KO mouse; AAV9-mediated mitochondria-targeted GSNOR overexpression; mitochondrial function assays Circulation research High 37377022
2015 ANT1 mutations (equivalent to adPEO and cardiomyopathy/myopathy mutations) cause protein misfolding in the yeast inner membrane, which disrupts the assembly and stability of multiple protein complexes in the membrane; adPEO-type mutations additionally form large aggregates whereas cardiomyopathy/myopathy-type mutations do not, suggesting these diseases belong to protein misfolding disorders. Yeast Aac2 mutagenesis; native gel electrophoresis of membrane complexes; pulse-chase analysis; fluorescence microscopy of aggregate formation Molecular biology of the cell Medium 25833713
2016 ANT1 confers sensitivity of the mitochondrial permeability transition (mPT) pore to the proton electrochemical gradient: cells lacking ANT1 are resistant to Ca2+- and H2O2-induced mitochondrial swelling despite greater membrane potential losses, and permeabilized ANT1-null myotubes show higher calcium uptake capacity and voltage-thresholds of mPT opening. mPT onset assessment by mitochondrial volume measurement ('thinness ratio', cobalt-calcein) in ANT1-deficient human fibroblasts and ANT1-knockdown C2C12 myotubes; Ca2+ measurement by X-rhod-1 and 4mtD3cpv biosensor; cytochrome c release assay Scientific reports Medium 27221760
2018 De novo dominant ANT1 (SLC25A4) mutations (R80H, R235G) classified as gain-of-function in yeast: introduction into yeast AAC2 in heteroallelic strains (mimicking human heterozygosity) caused more severe OXPHOS phenotypes than the hemiallelic strain, demonstrating gain-of-function dominance rather than haploinsufficiency. Yeast mutagenesis of AAC2 at equivalent positions; phenotypic characterization of hemiallelic vs heteroallelic yeast strains; respiratory growth assay Biochemical and biophysical research communications Medium 28947214
2017 NF-κB binds to two NF-κB responsive elements in the ANT1 promoter (+1 to +20 bp and +41 to +61 bp) and represses ANT1 transcription; TNFα-induced NF-κB activation suppresses ANT1 mRNA and protein, impairs ATP/ADP exchange, decreases ATP production, decreases calcium-induced mPTP opening, elevates mitochondrial potential, and increases ROS production. Promoter reporter assay; chromatin immunoprecipitation (ChIP); TNFα stimulation; RT-PCR and western blot; mitochondrial ATP/ADP exchange assay; mitochondrial membrane potential and ROS measurement Scientific reports Medium 28877317
2004 ANT1 overexpression induces apoptosis by recruiting the IκBα-NF-κB complex to mitochondria, coincident with decreased nuclear NF-κB DNA binding activity, downregulation of anti-apoptotic NF-κB target genes (Bcl-XL, MnSOD2, c-IAP2), and sensitization to apoptosis. ANT2 overexpression does not cause this effect, demonstrating isoform specificity. ANT1 overexpression; subcellular fractionation; western blot for IκBα/NF-κB in mitochondria; NF-κB EMSA (DNA binding); gene expression analysis; apoptosis assays; p65 co-expression rescue experiment The Journal of biological chemistry Medium 15231833
2006 ANT1 isoform, but not ANT2, is responsible for a significant fraction of the high basal proton leak (CAtr-sensitive) in brown-fat mitochondria; ANT2 mediates fatty acid-induced uncoupling in liver mitochondria. Brown adipose tissue expresses both Ant1 and Ant2 mRNA equally, whereas liver expresses only Ant2. Carboxyatractyloside (CAtr) inhibitor experiments on isolated brown-fat and liver mitochondria from wild-type and UCP1−/− mice; respiration measurement; isoform-specific mRNA expression by RT-PCR The Biochemical journal Medium 16831128
2016 ANT1 activity mediates fatty acid-induced uncoupling in skeletal muscle mitochondria. siRNA-mediated ANT1 knockdown in C2C12 myotubes decreased sensitivity to palmitate-induced uncoupling and impaired insulin-stimulated glucose uptake; in ZDF rat mitochondria, reduced FA-induced uncoupling was abolished by the ANT inhibitor carboxyatractyloside. siRNA knockdown of ANT1 in C2C12 myotubes; mitochondrial respiration assay with oleate/palmitate titration; carboxyatractyloside inhibitor experiment on ZDF rat skeletal muscle mitochondria; insulin-stimulated glucose uptake assay Diabetologia Medium 26886198
2010 PGC-1α-induced upregulation of ANT1 mediates increased susceptibility to ischemia-reperfusion injury in cardiomyocytes: siRNA knockdown of ANT1 abolished the detrimental effect of PGC-1α overexpression on cell death during anoxia-reoxygenation and preserved mitochondrial membrane potential under H2O2 stress. Adenoviral PGC-1α overexpression in H9c2 cells; Affymetrix gene array; siRNA knockdown of ANT1; anoxia-reoxygenation injury; mitochondrial membrane potential assay; Langendorff perfusion of PGC-1α transgenic mouse hearts Journal of molecular and cellular cardiology Medium 20600099
2010 MeCP2 interacts with YY1 and together they repress ANT1 gene transcription; loss of MeCP2 leads to increased ANT1 mRNA and protein levels in human and mouse cell lines, Rett patient fibroblasts, and Mecp2-null mouse brain. Co-immunoprecipitation (MeCP2-YY1 interaction in vitro and in vivo); ANT1 promoter-reporter assay; RT-PCR and western blot in MeCP2-null cells and Mecp2-null mouse brain Human molecular genetics Medium 20504995
2009 In Podospora anserina, adPEO-equivalent ANT1 mutations (A114P, L98P, V289M) dominantly cause decreased mitochondrial inner membrane potential, decreased ROS production, and accumulation of large-scale mtDNA deletions. Suppression of mtDNA instability from M106P and A121P mutations was achieved without restoration of membrane potential, indicating mtDNA instability is not solely caused by reduced membrane potential or altered ROS. Fungal genetics (Podospora anserina); dominant mutation introduction; membrane potential measurement; ROS assay; mtDNA deletion analysis; suppressor genetics (rmp1 and AS1 alleles) Genetics Medium 19687137
2022 Oxidative stress-induced changes in lipid shape (PE adducts, lysolipids) decrease the stored curvature elastic stress (SCES) of the lipid bilayer membrane, which increases the protonophoric activity of ANT1 (and UCP1); ANT1 senses membrane curvature elastic stress to regulate H+ transport. Planar lipid bilayer electrophysiology with ANT1; lipid composition manipulation (OPC, MPC, PE adducts); molecular dynamics simulations of lateral pressure profiles Antioxidants (Basel, Switzerland) Medium 36552523
2018 Brain-specific Ant1 heterozygous conditional knockout mice show hyperexcitability of dorsal raphe serotonergic neurons, enhanced serotonin turnover in the nucleus accumbens, upregulation of Maob in dorsal raphe, and accumulation of COX-negative cells in dorsal raphe, linking ANT1 mitochondrial dysfunction to serotonergic dysregulation. Conditional brain-specific Ant1 heterozygous knockout mice; behavioral analysis (IntelliCage, 5-CSRTT); electrophysiology of dorsal raphe neurons; serotonin turnover measurement; immunohistochemistry for COX-negative cells; Maob expression analysis Molecular psychiatry Medium 29892051
2011 Complete loss of ANT1 expression (homozygous splice-site mutation) in a patient causes a clinical syndrome of cardiomyopathy and myopathy, with dramatic mitochondrial proliferation, multiple mtDNA deletions, and abnormal metabolic profile; no compensatory increase in ANT3 transcript was observed. Patient molecular diagnosis; RT-PCR showing absent ANT1 transcript; metabolic profiling; muscle biopsy histology; ANT3 expression measurement Journal of medical genetics Medium 22187496
2018 A de novo dominant SLC25A4 variant (p.Lys33Gln) expressed in Lactococcus lactis membrane vesicles shows significantly impaired ADP/ATP transport, establishing loss of transport function as the pathogenic mechanism; patient muscle shows decreased complex I, III, and IV protein levels with largely unaffected total AAC content. Expression of mutant AAC1 in Lactococcus lactis; transport assay with fused membrane vesicles; immunohistochemistry and western blot of patient muscle Neurology. Genetics Medium 30046662
2022 ANT1 acts upstream of the PINK1/Parkin mitophagy pathway: BaP/BPDE exposure suppresses ANT1 expression, leading to decreased PINK1 bound to the outer mitochondrial membrane and reduced Parkin recruitment, thereby impairing mitophagy in ovarian corpus luteum cells. Overexpression of ANT1 partially restores mitophagy and mitochondrial function. In vivo mouse exposure and in vitro KGN cell treatment with BaP/BPDE; ANT1 overexpression; PINK1/Parkin immunofluorescence and western blot; mitochondrial membrane potential and ATP measurement The Science of the total environment Medium 34986425
2025 USP34 deubiquitinates and stabilizes ANT1 protein, thereby promoting PINK1/Parkin-dependent mitophagy in chondrocytes; chondrocyte-specific Usp34 knockout mice develop age-dependent temporomandibular joint osteoarthritis, and USP34 deficiency exacerbates mechanical stress-induced degeneration. Chondrocyte-specific Usp34 knockout mice; co-immunoprecipitation (USP34-ANT1); ubiquitination assay; mitophagy assay; histological analysis of TMJ cartilage JBMR plus Medium 41631201
2014 Drosophila sesB (ANT ortholog) mutant adults show decreased respiratory control ratio, downregulation of cytochrome oxidase, ATP depletion, lactate accumulation, and a metabolic shift toward glycolysis. Female sterility is substantially rescued by somatic expression of alternative oxidase (AOX), while developmental delay was alleviated by an altered mitochondrial DNA background. Bioenergetic analysis of sesB1 mitochondria (respiratory control ratio, COX activity); metabolomics (ATP, lactate); gene expression analysis; AOX transgenic rescue; mtDNA background substitution Disease models & mechanisms Medium 24812436
1992 The human muscle adenine nucleotide translocator gene (ANT1) is localized to chromosome 4q35 by fluorescence in situ hybridization. Fluorescence in situ hybridization (FISH) Cytogenetics and cell genetics Medium 1582253
2025 Restoration of just ~10% of Ant1 gene expression via AAV2/9 delivery in neonatal Ant1−/− and Ant1−/−+ND6P25L mouse hearts was sufficient to ameliorate cardiomyopathy, reversing dysregulated mitochondrial metabolic genes including PGC1α, cardiac contractile proteins, and extracellular matrix proteins. AAV2/9-mediated ANT1 cDNA delivery in Ant1 null mice; proteomics; single-nucleus RNA sequencing; cardiac functional analysis Nature communications Medium 41398158
2018 ANT1 knockdown in macrophages reduces IL-6 expression after LPS stimulation; JNK signaling upstream of IL-6 is downregulated by ANT1 loss, while NF-κB signaling and other MAP kinases remain unchanged, placing ANT1 specifically in the JNK-IL-6 axis. ANT1 siRNA knockdown in macrophages; LPS stimulation; cytokine measurement; western blot for JNK, NF-κB, and MAP kinases FEBS letters Low 30311946
2025 Misfolding of mutant ANT1 (AAC2 in yeast) clogs TOM and TIM22 protein import complexes, inducing mitochondrial Precursor Overaccumulation Stress (mPOS) in the cytosol; MFB1 (mitochondrial F-box protein) overexpression suppresses growth defects from a clogger allele of AAC2, and its disruption exacerbates import clogging, suggesting MFB1 maintains import competency under ANT1 clogging conditions. Yeast genetics; BioID proximity labeling (Mfb1-Tom22 interaction); cell growth assay; cytosolic protein retention measurement bioRxivpreprint Low bio_10.1101_2025.10.13.682092

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis. Nature communications 128 29255148
2003 Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). Neurology 123 12707443
2016 Recurrent De Novo Dominant Mutations in SLC25A4 Cause Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number. American journal of human genetics 91 27693233
2003 Autosomal dominant external ophthalmoplegia and bipolar affective disorder associated with a mutation in the ANT1 gene. Neuromuscular disorders : NMD 86 12565915
2004 Recruitment of NF-kappaB into mitochondria is involved in adenine nucleotide translocase 1 (ANT1)-induced apoptosis. The Journal of biological chemistry 81 15231833
2006 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. The Biochemical journal 77 16831128
2004 Mutations in AAC2, equivalent to human adPEO-associated ANT1 mutations, lead to defective oxidative phosphorylation in Saccharomyces cerevisiae and affect mitochondrial DNA stability. Human molecular genetics 71 15016764
2005 A novel ANT1 gene mutation with probable germline mosaicism in autosomal dominant progressive external ophthalmoplegia. Neuromuscular disorders : NMD 56 15792871
2011 Complete loss of expression of the ANT1 gene causing cardiomyopathy and myopathy. Journal of medical genetics 55 22187496
2008 Over-expression of adenine nucleotide translocase 1 (ANT1) induces apoptosis and tumor regression in vivo. BMC cancer 55 18522758
2010 The MeCP2/YY1 interaction regulates ANT1 expression at 4q35: novel hints for Rett syndrome pathogenesis. Human molecular genetics 48 20504995
2023 Mitochondrial GSNOR Alleviates Cardiac Dysfunction via ANT1 Denitrosylation. Circulation research 47 37377022
2006 Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay. European journal of human genetics : EJHG 41 16639411
2005 The adenine nucleotide translocase type 1 (ANT1): a new factor in mitochondrial disease. IUBMB life 41 16203679
2015 Isolation of candidate genes for the barley Ant1 and wheat Rc genes controlling anthocyanin pigmentation in different vegetative tissues. Molecular genetics and genomics : MGG 39 25585663
1995 The isolation of Ant1, a transposable element from Aspergillus niger. Molecular & general genetics : MGG 37 8552048
2021 ANT1 Activation and Inhibition Patterns Support the Fatty Acid Cycling Mechanism for Proton Transport. International journal of molecular sciences 36 33801254
2018 Ant1 mutant mice bridge the mitochondrial and serotonergic dysfunctions in bipolar disorder. Molecular psychiatry 35 29892051
2008 A functional role for 4qA/B in the structural rearrangement of the 4q35 region and in the regulation of FRG1 and ANT1 in facioscapulohumeral dystrophy. PloS one 35 18852887
2023 Loss of ANT1 Increases Fibrosis and Epithelial Cell Senescence in Idiopathic Pulmonary Fibrosis. American journal of respiratory cell and molecular biology 32 37487137
2017 Transcription factor NF-kappa B represses ANT1 transcription and leads to mitochondrial dysfunctions. Scientific reports 32 28317877
2011 adPEO mutations in ANT1 impair ADP-ATP translocation in muscle mitochondria. Human molecular genetics 32 21586654
2010 Transient upregulation of PGC-1alpha diminishes cardiac ischemia tolerance via upregulation of ANT1. Journal of molecular and cellular cardiology 31 20600099
2014 Phenotypic rescue of a Drosophila model of mitochondrial ANT1 disease. Disease models & mechanisms 29 24812436
2016 ANT1-mediated fatty acid-induced uncoupling as a target for improving myocellular insulin sensitivity. Diabetologia 28 26886198
2016 Alterations in voltage-sensing of the mitochondrial permeability transition pore in ANT1-deficient cells. Scientific reports 28 27221760
2015 Two Novel Mutations in the SLC25A4 Gene in a Patient with Mitochondrial Myopathy. JIMD reports 26 25732997
2010 Retinal function and structure in Ant1-deficient mice. Investigative ophthalmology & visual science 22 20671283
2006 POLG1, C10ORF2, and ANT1 mutations are uncommon in sporadic progressive external ophthalmoplegia with multiple mitochondrial DNA deletions. Neurology 22 16682683
2015 Misfolding of mutant adenine nucleotide translocase in yeast supports a novel mechanism of Ant1-induced muscle diseases. Molecular biology of the cell 21 25833713
2018 Expanding the phenotype of de novo SLC25A4-linked mitochondrial disease to include mild myopathy. Neurology. Genetics 20 30046662
2020 Evaluation of the Diagnostic and Predictive Value of Serum Levels of ANT1, ATG5, and Parkin in Multiple Sclerosis. Clinical neurology and neurosurgery 18 32890892
2012 A study of PKM2, PFK-1, and ANT1 expressions in cervical biopsy tissues in China. Medical oncology (Northwood, London, England) 18 22227854
2005 Eliminating the Ant1 isoform produces a mouse with CPEO pathology but normal ocular motility. Investigative ophthalmology & visual science 18 16303948
2023 FA Sliding as the Mechanism for the ANT1-Mediated Fatty Acid Anion Transport in Lipid Bilayers. International journal of molecular sciences 17 37762012
2017 Two new cases of mitochondrial myopathy with exercise intolerance, hyperlactatemia and cardiomyopathy, caused by recessive SLC25A4 mutations. Mitochondrion 16 28823815
2006 Mutation D104G in ANT1 gene: complementation study in Saccharomyces cerevisiae as a model system. Biochemical and biophysical research communications 16 16438935
1999 Estrogen stimulates expression of adenine nucleotide translocator ANT1 messenger RNA in female rat hearts. Molecular and cellular endocrinology 16 10411310
2002 The peroxisomal transporter gene ANT1 is regulated by a deviant oleate response element (ORE): characterization of the signal for fatty acid induction. The Biochemical journal 15 12071844
2024 Single-cell transcriptomics in MI identify Slc25a4 as a new modulator of mitochondrial malfunction and apoptosis-associated cardiomyocyte subcluster. Scientific reports 14 38654053
2022 Exposure to benzo(a)pyrene suppresses mitophagy via ANT1-PINK1-Parkin pathway in ovarian corpus luteum during early pregnancy. The Science of the total environment 13 34986425
2020 Low expression of ANT1 confers oncogenic properties to rhabdomyosarcoma tumor cells by modulating metabolism and death pathways. Cell death discovery 13 32728477
2017 Mitochondrial ANT-1 related adPEO leading to cognitive impairment: is there a link? Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 13 28690391
2015 ZNF555 protein binds to transcriptional activator site of 4qA allele and ANT1: potential implication in Facioscapulohumeral dystrophy. Nucleic acids research 13 26184877
2011 SLC25A4 and C10ORF2 Mutations in Autosomal Dominant Progressive External Ophthalmoplegia. Journal of clinical neurology (Seoul, Korea) 13 21519523
2021 Manipulating a Single Transcription Factor, Ant1, Promotes Anthocyanin Accumulation in Barley Grains. Journal of agricultural and food chemistry 12 33908247
2021 A Yeast-Based Screening Unravels Potential Therapeutic Molecules for Mitochondrial Diseases Associated with Dominant ANT1 Mutations. International journal of molecular sciences 12 33923309
2009 Suppression of mitochondrial DNA instability of autosomal dominant forms of progressive external ophthalmoplegia-associated ANT1 mutations in Podospora anserina. Genetics 12 19687137
1992 Assignment of the human muscle adenine nucleotide translocator gene (ANT1) to 4q35 by fluorescence in situ hybridization. Cytogenetics and cell genetics 12 1582253
2022 Porcine β-defensin 2 confers enhanced resistance to swine flu infection in transgenic pigs and alleviates swine influenza virus-induced apoptosis possibly through interacting with host SLC25A4. Antiviral research 11 35341807
2018 Muscle Weakness, Cardiomyopathy, and L-2-Hydroxyglutaric Aciduria Associated with a Novel Recessive SLC25A4 Mutation. JIMD reports 11 29654543
2015 Genetic linkage facilitates cloning of Ert-m regulating plant architecture in barley and identified a strong candidate of Ant1 involved in anthocyanin biosynthesis. Plant molecular biology 11 26228300
2022 ANT1 overexpression models: Some similarities with facioscapulohumeral muscular dystrophy. Redox biology 10 36030628
2022 Promoter replacement of ANT1 induces anthocyanin accumulation and triggers the shade avoidance response through developmental, physiological and metabolic reprogramming in tomato. Horticulture research 10 36751272
2022 Membrane Lipid Reshaping Underlies Oxidative Stress Sensing by the Mitochondrial Proteins UCP1 and ANT1. Antioxidants (Basel, Switzerland) 8 36552523
2018 Phenotypic spectrum of SLC25A4 mutations. Biomedical reports 8 30013777
2017 Dominance of yeast aac2R96H and aac2R252G mutations, equivalent to pathological mutations in ant1, is due to gain of function. Biochemical and biophysical research communications 8 28947214
2012 ANT1 is reduced in sporadic inclusion body myositis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 8 22350218
2016 ER-localized adenine nucleotide transporter ER-ANT1: an integrator of energy and stress signaling in rice. Plant molecular biology 7 27614468
2014 Extracellular ADP prevents neuronal apoptosis via activation of cell antioxidant enzymes and protection of mitochondrial ANT-1. Biochimica et biophysica acta 7 24709060
2025 ANT1 Deficiency Impairs Macrophage Metabolism and Migration, Protecting Against Emphysema in Chronic Obstructive Pulmonary Disease. American journal of respiratory cell and molecular biology 6 40439531
2021 Mitochondrial DNA depletion syndrome with a mutation in SLC25A4 developing epileptic encephalopathy: A case report. Brain & development 6 34452803
2006 Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor. Biochemical and biophysical research communications 6 16414017
2009 Isolation, nucleotide identification and tissue expression of three novel ovine genes-SLC25A4, SLC25A5 and SLC25A6. Molecular biology reports 5 19763879
2009 [Expression of genes psma6 and slc25a4 in patients with acute monocytic leukemia]. Zhongguo shi yan xue ye xue za zhi 5 19840444
1998 Muscle/heart isoform of mitochondrial adenine nucleotide translocase (ANT1) is transiently expressed during perinatal development in rat liver. FEBS letters 5 9468308
2021 Adipose-derived mesenchymal stem cells preserve cardiac function via ANT-1 in dilated cardiomyopathy hamster model. Regenerative therapy 4 34307796
2011 The respiratory-dependent assembly of ANT1 differentially regulates Bax and Ca2+ mediated cytochrome c release. Frontiers in bioscience (Elite edition) 4 21196320
2023 Possible Participation of Adenine Nucleotide Translocase ANT1 in the Cytotoxic Action of Progestins, Glucocorticoids, and Diclofenac on Tumor Cells. Pharmaceutics 3 38140127
2018 The inner mitochondrial membrane protein ANT1 modulates IL-6 expression via the JNK pathway in macrophages. FEBS letters 3 30311946
2025 Hypertension Increases Susceptibility to Lead-Induced Microglial Polarization via ANT1-Mediated Mitochondrial DNA/cGAS/STING Signaling. Research (Washington, D.C.) 2 41404489
2024 CD147 mitochondria translocation induced airway remodeling in asthmatic mouse models by regulating M2 macrophage polarization via ANT1-mediated mitophagy. American journal of physiology. Cell physiology 2 39740799
2022 Kearns-Sayre syndrome with rare imaging finding of SLC25A4 Mutation. Neurosciences (Riyadh, Saudi Arabia) 2 35477912
2026 USP34 attenuates cartilage degradation in temporomandibular joint osteoarthritis by ANT1-mediated mitophagy. JBMR plus 1 41631201
2025 Partial restoration of mitochondrial dysfunction by AAV-Ant1 protects from dilated cardiomyopathy in Ant1-/- plus mtDNA mutant mice. Nature communications 1 41398158
2025 Targeting ANT1 to regulate PINK1/Parkin-mediated mitophagy is an effective treatment of trauma-induced tendon heterotopic ossification. Journal of orthopaedic translation 1 41542093
2024 Optical redox imaging of ANT1-deficient muscles. Journal of innovative optical health sciences 1 39077370
2009 [Association of the T(-365)C POLG1, G(-25)A ANT1 and G(-605)T PEO1 gene polymorphisms with diabetic polyneuropathy in patients with type 1 diabetes mellitus]. Molekuliarnaia biologiia 1 19425506
2026 Histone H3K27 acetylation of slc25a4 mediates triclocarban-induced transgenerational developmental toxicity in zebrafish (Danio rerio) at subthreshold exposure. Environmental research 0 41687846
2026 Gut microbiota-derived trimethylamine N-oxide contributes to cardiomyocyte pyroptosis and cardiac injury via the tRF-Glu-ANT1-GSDMD axis. Cellular & molecular biology letters 0 41735825
2026 CFAP251 Deficiency Induces Male Infertility and PCD-like Ciliary Defects by Disrupting TUBB4B and SLC25A4 Recruitment in Humans and Mice. International journal of biological sciences 0 41943837
2026 Progression of human osteosarcoma with altered ANT1/SLC25a4 expression. Kansas journal of medicine 0 42137380
2026 Isovitexin Alleviates Myocardial Ischemia by Targeting SLC25A4 and Modulating the AMPK/PGC-1α Signaling Pathway. International journal of molecular sciences 0 42196177
2025 An integrated bioinformatic investigation of succinic acid metabolism related genes in ccRCC followed by preliminary validation of SLC25A4 in tumorigenesis. Scientific reports 0 40473684
2025 Exploring ANT1 dysfunction as a pathological driver of wooden breast myopathy in broiler chickens. Poultry science 0 40972420
2025 Reduced Mitochondrial Adenine Nucleotide Translocase 1 (ANT1) Correlates With Aging-Associated Airway Remodeling. Aging cell 0 41074556
2025 ANT1 suppression inhibits the progression of colorectal cancer by suppressing PINK1/Parkin-mediated mitophagy. Acta biochimica et biophysica Sinica 0 41185561
2025 S-adenosylmethionine and nicotinic acid suppress Hepatocellular carcinoma proliferation by targeting SLC25A4. Biochemical pharmacology 0 41213409
2025 Wheat SLC25A4-7B negatively regulates drought tolerance by coordinating stomatal aperture size and abscisic acid content. Planta 0 41342959
2023 Construction of a high-density genetic map for yardlong bean and identification of ANT1 as a regulator of anthocyanin biosynthesis. Horticulture research 0 38274647

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