Affinage

MT-ATP6

ATP synthase F(0) complex subunit a · UniProt P00846

Length
226 aa
Mass
24.8 kDa
Annotated
2026-06-10
100 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MT-ATP6 encodes subunit a of the mitochondrial F1F0-ATP synthase (complex V), where it cooperates with the c-ring to form the proton-translocation pathway that couples the inner-membrane proton gradient to ATP synthesis (PMID:8078883, PMID:10403398). Cybrid reconstitution of the m.8993T>G mutation established that pathogenic substitutions impair H+-translocating ATP synthase function, reducing ADP-stimulated respiration and ATP synthesis turnover without preventing correct assembly or oligomerization of the holoenzyme, so the primary defect is functional inhibition of a properly assembled enzyme that is additionally destabilized under denaturing stress (PMID:8078883, PMID:17121862). Mutagenesis of equivalent residues in bacterial and yeast subunit a maps this defect to the proton-conduction machinery: pathogenic arginine and proline substitutions disrupt the salt-bridge relay between subunit-a arginines and the c-ring glutamate that normally drives proton movement across the membrane (PMID:10403398, PMID:31181185). A second class of variants — frameshift, truncating, and stop/cleavage-site mutations — acts post-transcriptionally to deplete subunit a protein and biosynthesis, producing assembly-incompetent ATPase subcomplexes that retain hydrolytic but not synthetic activity (PMID:15265003, PMID:28412374, PMID:32042910). Allotopic and modified-mRNA expression of recoded MT-ATP6 from the nucleus is imported, processed, incorporated into complex V, and rescues ATP synthesis in m.8993T>G cybrids, with co-expression of MT-ATP8 required for full hydrolysis and respiration (PMID:11925565, PMID:27596602, PMID:29539412). The downstream consequences of these defects include cristae disruption, ROS overproduction, defective glycolytic reprogramming, and disease ranging from NARP/MILS to isolated axonal Charcot-Marie-Tooth neuropathy, with the mtDNA haplogroup background modulating biochemical severity (PMID:17568559, PMID:19875463, PMID:22933740, PMID:29602698). Beyond the synthase itself, mitochondria-targeted miR-378a negatively regulates subunit a abundance in the diabetic heart through a Kcnq1ot1/miR-378a axis (PMID:35108116).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 High

    Established that an MT-ATP6 point mutation, not nuclear background, is the direct cause of defective mitochondrial ATP synthase function, anchoring the gene's bioenergetic role.

    Evidence Cybrid generation of homoplasmic m.8993T>G cells with respiration and ADP/O measurements

    PMID:8078883

    Open questions at the time
    • Did not resolve which step of the catalytic/proton cycle is impaired
    • Single mutation tested
  2. 1999 High

    Localized the functional lesion of pathogenic MT-ATP6 variants to the proton-translocation and ATP-synthesis activity of subunit a by reconstructing equivalent mutations in bacterial enzyme.

    Evidence Site-directed mutagenesis of E. coli atp6 a subunit with ATP synthesis, ATPase, DCCD-sensitivity and proton-pumping assays

    PMID:10403398

    Open questions at the time
    • Bacterial surrogate, not human enzyme
    • Did not address human complex assembly
  3. 2004 High

    Showed a distinct, post-transcriptional class of MT-ATP6 lesion in which loss of subunit a protein destabilizes the synthase into hydrolysis-only subcomplexes and impairs COX assembly.

    Evidence 35S-methionine labeling, BN-PAGE/2D gels, ATP synthesis/hydrolysis, Northern blot of a 9205ΔTA stop/cleavage-site deletion

    PMID:15265003

    Open questions at the time
    • Mechanism of COX co-assembly defect not resolved
    • Single variant
  4. 2006 High

    Defined the primary pathogenic mechanism of m.8993 alleles as functional inhibition of a correctly assembled enzyme rather than disassembly, with destabilization only under stress.

    Evidence Immunoprecipitation, BN-PAGE, ATP synthesis turnover and oligomycin sensitivity assays under denaturing conditions

    PMID:17121862

    Open questions at the time
    • Did not separate proton-pumping from catalytic contributions
    • Stress conditions in vitro
  5. 2007 Medium

    Revealed that two mutations at the same nucleotide produce divergent downstream pathology — energy deficiency versus ROS overproduction — indicating allele-specific mechanisms.

    Evidence ATP synthesis and ROS measurements in patient lymphocytes comparing m.8993T>G and T>C

    PMID:17568559

    Open questions at the time
    • No cybrid controls to exclude nuclear/background effects
    • ROS source not mapped to a specific complex
  6. 2009 High

    Demonstrated that the mtDNA haplogroup background modifies the biochemical severity of MT-ATP6 mutations, explaining clinical variability.

    Evidence Five patient cybrid lines with ATP synthesis, oxygen consumption, BN-PAGE and full mtDNA sequencing

    PMID:19875463

    Open questions at the time
    • Did not establish causal contribution of each individual background variant
    • Limited number of haplotypes
  7. 2016 High

    Established that overlapping MT-ATP6/MT-ATP8 region mutations disrupt complex V biogenesis, and that both subunit a and subunit ATP8 products are required for full enzyme function.

    Evidence BN-PAGE of complex V assembly intermediates and ATP assays in patient myoblasts; allotopic co-expression of ATP6 and ATP8 rescue in null cybrids

    PMID:27502083 PMID:27596602

    Open questions at the time
    • Stoichiometric/structural role of each subunit in assembly not fully resolved
  8. 2012 Medium

    Extended the disease spectrum by showing MT-ATP6 mutations can cause isolated axonal neuropathy through impaired complex V assembly and activity.

    Evidence BN-PAGE for complex V structure/activity and mutation-load quantification in CMT2 patients (m.9185T>C)

    PMID:22933740

    Open questions at the time
    • Tissue-specific basis of axonal vulnerability not addressed
    • Single-lab structural assessment
  9. 2018 Medium

    Connected the molecular defect to cellular energy reprogramming, showing m.8993T>G impairs cristae structure and the ability to switch to glycolysis under OXPHOS inhibition.

    Evidence Cristae morphometry, Seahorse respirometry and glycolysis stress assays in patient fibroblasts

    PMID:29602698

    Open questions at the time
    • Single patient
    • Causal link between cristae change and metabolic inflexibility not dissected
  10. 2018 High

    Demonstrated that nuclear/cytoplasmic delivery of MT-ATP6 (allotopic protein and modified mRNA) can rescue the ATP synthesis defect, providing a therapeutic-mechanism proof of concept.

    Evidence Allotopic recoded MT-ATP6 expression with import/processing/assembly and ATP synthesis rescue; modified-mRNA screening of MTS/3'UTRs with functional rescue in m.8993T>G cybrids

    PMID:11925565 PMID:29539412

    Open questions at the time
    • Efficiency and in vivo applicability not established
    • Long-term complex V stability after import not assessed
  11. 2019 High

    Resolved at atomic resolution how a pathogenic subunit-a substitution blocks proton translocation by rerouting the arginine/glutamate salt-bridge relay.

    Evidence Yeast aW126R model with compensatory mutagenesis at aR169 and structural analysis (m.8851T>C / aW109R)

    PMID:31181185

    Open questions at the time
    • Generalization to other patient alleles not tested
    • Yeast surrogate
  12. 2022 Medium

    Linked truncating MT-ATP6 mutations to developmental signaling, showing assembly failure and cristae disruption that drive Notch hyperactivation and blocked motor neuron differentiation.

    Evidence Patient iPSC-derived motor neurons with assembly, cristae, Notch activity, metabolic flux assays and molecular dynamics of the a/c subcomplex (m.9154C>T)

    PMID:34635923

    Open questions at the time
    • Mechanistic link from energy defect to Notch not biochemically resolved
    • Single mutation/cell model
  13. 2022 Medium

    Identified post-transcriptional control of subunit a abundance via a mitochondria-targeted microRNA, defining a Kcnq1ot1/miR-378a/mt-ATP6 regulatory axis relevant to diabetic cardiomyopathy.

    Evidence miR-378a knockout T2DM mouse and Kcnq1ot1 overexpression in HL-1 cardiomyocytes with ATP synthase activity, Western blot and cardiac function

    PMID:35108116

    Open questions at the time
    • Direct miR-378a:mt-ATP6 mRNA interaction within mitochondria not structurally mapped
    • Human relevance not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How tissue-specific phenotypes (neuropathy vs. encephalopathy vs. cardiomyopathy) arise from the same biochemical synthase defect remains unresolved.
  • No unifying model linking heteroplasmy level, downstream signaling, and cell-type vulnerability
  • Limited in vivo mechanistic data for non-canonical phenotypes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0005215 transporter activity 3
Localization
GO:0005739 mitochondrion 4
Pathway
R-HSA-1430728 Metabolism 4
Partners
MT-ATP8
Complex memberships
F1F0-ATP synthase (complex V)

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 The mtDNA nt 8993 T→G mutation in the ATP6 gene (encoding ATPase 6 subunit of complex V) directly causes defective mitochondrial H⁺-translocating ATP synthase function: cybrid cells homoplasmic for the mutation showed 24–53% reduction in ADP-stimulated (state III) respiration and 30% decrease in ADP/O ratio, while DNP-uncoupled respiration remained normal, demonstrating the biochemical defect is linked specifically to this mutation and not to nuclear background. Cytoplast transfer to mtDNA-deficient (rho0) cells (cybrid generation), mitochondrial respiration assays with multiple substrates, ADP/O ratio measurements Proceedings of the National Academy of Sciences of the United States of America High 8078883
1999 Site-directed mutagenesis of equivalent residues in the E. coli ATP synthase a subunit showed that the L262P mutation (equivalent to human m.9185T>C) caused ~70% loss of ATP synthesis activity, reduced DCCD sensitivity, and lowered proton pumping activity; L207P (equivalent to m.8993T>C) reduced ATP synthesis by ~50% and affected DCCD sensitivity with only marginal effect on proton pumping. This confirmed that MT-ATP6 pathogenic mutations impair the proton-translocation and ATP synthesis functions of subunit a. Site-directed mutagenesis of E. coli atp6 a subunit, in vitro ATPase activity assays, ATP synthesis assays, proton pumping assays (AMCA quenching) FEBS letters High 10403398
2002 Wild-type MT-ATP6 protein can be allotopically expressed from the nucleus: a recoded ATPase 6 gene (universal genetic code) with an appended N-terminal mitochondrial targeting signal and C-terminal FLAG tag was expressed in human cells, the precursor was imported into and processed within mitochondria, incorporated into complex V, and rescued ATP synthesis in cybrids homoplasmic for the m.8993T>G mutation. This is the first demonstration of allotopic expression of an mtDNA-encoded polypeptide in mammalian cells. Nuclear transfection of recoded MT-ATP6 construct, mitochondrial import/processing assay, FLAG-tag detection, ATP synthesis assay in cybrids, selective medium growth recovery Nature genetics High 11925565
2006 Homoplasmic T8993G and T8993C mutations in MT-ATP6 inhibit ATP synthesis (T8993G causes ~60% inhibition in ATP synthesis turnover) and destabilize the F1F0 complex under denaturing conditions, but do not prevent correct assembly or oligomerization of the ATP synthase. The primary pathogenic mechanism is functional inhibition of a correctly assembled enzyme, not disassembly. Immunoprecipitation, blue-native gel electrophoresis, ATP synthesis turnover assay, oligomycin sensitivity assay, in vitro denaturing conditions The Journal of biological chemistry High 17121862
2007 Both m.8993T>G and m.8993T>C mutations in MT-ATP6 lead to energy deprivation and ROS overproduction in patient lymphocytes, but with different relative contributions: T>G primarily induces energy deficiency, while T>C predominantly favors increased ROS production, indicating different pathogenic mechanisms for two mutations at the same nucleotide affecting Leu-156 of ATPase 6. Mitochondrial functional assays in patient lymphocytes (ATP synthesis, ROS measurement), comparison of T>G vs. T>C mutation carriers Biochimica et biophysica acta Medium 17568559
2009 The mtDNA background modulates bioenergetic defects in NARP/MILS ATP6 mutant cells: cybrids from patients with T8993G, T8993C, or T9176G mutations showed dramatically variable ATP synthesis impairment, and the most severe cases also exhibited defective respiration and disassembly of respiratory chain complexes. Full mtDNA sequencing identified background variants in structural genes causing amino acid changes that destabilize the respiratory chain, demonstrating that mtDNA haplogroup background modifies the biochemical severity of MT-ATP6 mutations. Cybrid cell lines from five patients, ATP synthesis assay, oxygen consumption measurement, BN-PAGE for respiratory chain complex assembly, full mtDNA sequencing Human molecular genetics High 19875463
2004 A 2 bp deletion (9205ΔTA) affecting the stop codon of the MT-ATP6 gene and the cleavage site between ATP6 and COX3 mRNAs causes a 10-fold decrease in subunit a content (ATPase 6 protein), 70% decrease in ATP synthesis, and 85% decrease in COX activity. [35S]-methionine labeling showed 9-fold decrease in subunit a biosynthesis. BN-PAGE revealed instability and dissociation of the ATPase complex into subcomplexes capable of hydrolysis but not synthesis, and impaired COX assembly. 35S-methionine metabolic labeling of mitochondrial translation products, BN-PAGE and 2D electrophoresis, ATP synthesis assay, ATPase hydrolysis assay, mitochondrial membrane potential measurement, Northern blot, quantitative RT-PCR The Biochemical journal High 15265003
2012 The m.9185T>C mutation in MT-ATP6 causes impaired assembly and reduced activity of the complex V holoenzyme, demonstrated by blue-native gel electrophoresis in patients with axonal Charcot-Marie-Tooth disease (CMT2), establishing that MT-ATP6 mutations can cause isolated axonal neuropathy via disruption of ATP synthase structure and function. Blue-native gel electrophoresis (BN-PAGE) for complex V structure and activity, restriction endonuclease analysis for mutation load quantification Neurology Medium 22933740
2016 Stable nuclear co-expression of both ATP8 and ATP6 genes (with mitochondrial targeting sequences) in a cybrid null for both proteins rescued Complex V assembly and function, restoring ATP hydrolysis/synthesis, oxygen consumption, and viability on Krebs cycle substrates. Nuclear expression of ATP8 alone restored viability and ATP synthesis but failed to restore ATP hydrolysis and was insensitive to OXPHOS inhibitors, demonstrating that both MT-ATP6 and MT-ATP8 protein products are required for full Complex V function. Stable nuclear transfection with allotopic constructs, ATP synthesis/hydrolysis assays, BN-PAGE for complex V assembly, oxygen consumption rate measurement, viability assay on Krebs cycle substrates, inhibitor sensitivity assays Nucleic acids research High 27596602
2017 A novel frameshift mutation in MT-ATP6 causes severe depletion of ATP6 protein and aberrant translation product accumulation (demonstrated by [35S]-methionine labeling), impairs complex V assembly (accumulation of ATPase subcomplexes on native PAGE), and causes isolated complex V deficiency with preserved ATP8/6 mRNA levels, showing that the frameshift acts post-transcriptionally to reduce ATP6 protein and disrupt complex V assembly. Metabolic 35S-labeling of mitochondrial translation products, Northern blotting, native PAGE with immunoblotting, enzymatic and oxymetric analysis of mitochondrial respiratory system European journal of medical genetics Medium 28412374
2018 The m.8993T>G variant in MT-ATP6 causes severe defects in mitochondrial cristae structure (morphometric analysis) and impairs oxidative phosphorylation with decreased spare respiratory capacity and a stunted ability to switch to glycolysis upon full OXPHOS inhibition, revealing a defective energy reprogramming mechanism in patient fibroblasts. Mitochondrial morphometric analysis (live-cell imaging of cristae), live-cell mitochondrial respiratory analysis (Seahorse XF), glycolysis stress assay Molecular genetics and metabolism Medium 29602698
2018 Chemically modified mRNAs encoding allotopically expressed MT-ATP6 with optimized mitochondrial targeting sequences functionally rescued mitochondrial function in cells harboring the m.8993T>G mutation, establishing that cytoplasmic translation of MT-ATP6 followed by mitochondrial import can rescue the ATP synthesis defect. Automated quantitative screening of 31 mitochondrial targeting sequences and 15 3'UTRs, protein localization assay, mitochondrial morphology assay, functional rescue assay in m.8993T>G cybrid cells Cell reports Medium 29539412
2019 The pathogenic m.8851T>C mutation (aW109R in subunit a of ATP synthase) prevents proper proton movement within the n-side hydrophilic cleft of the ATP synthase membrane domain. Using yeast equivalent (aW126R), compensatory mutagenesis and analysis of atomic structures showed that the arginine substitution causes electrostatic/steric hindrance that enables aR169 to form a salt bridge with cE59, preventing aR176 from properly interacting with cE59 and blocking proton translocation across the mitochondrial inner membrane. Yeast Saccharomyces cerevisiae model (equivalent aW126R mutation), site-directed mutagenesis (multiple compensatory mutations at aR169 and surrounding residues), ATP synthase assembly/stability analysis, functional ATP synthase assays, analysis of published atomic structures Biochimica et biophysica acta. Bioenergetics High 31181185
2016 The m.8561C>G mutation in the overlapping region of MT-ATP6/MT-ATP8 causes impaired complex V assembly (additional assembly intermediate and increased free F1 subcomplex by BN-PAGE) and decreased intracellular ATP concentration in patient myoblasts, demonstrating that mutations in the overlapping MT-ATP6/8 region disrupt both subunits and impair ATP synthase biogenesis. BN-PAGE to detect complex V assembly intermediates, intracellular ATP concentration measurement in patient myoblasts Journal of neurology Medium 27502083
2022 A heteroplasmic truncating mutation m.9154C>T in MT-ATP6 impairs ATP synthase assembly and disrupts mitochondrial cristae morphology. In patient-derived iPSC-derived motor neurons, the truncation causes Notch hyperactivation and impairs motor neuron differentiation beyond the progenitor stage, and at a lower heteroplasmy threshold causes a metabolic shift affecting lactate utilization. Molecular dynamics simulations predicted destabilization of the a/c subunit subcomplex consistent with the truncation. Patient-specific iPSC generation and motor neuron differentiation, ATP synthase assembly assay, mitochondrial cristae morphology analysis, Notch pathway activity measurement, metabolic flux analysis (lactate utilization), molecular dynamics simulation Human molecular genetics Medium 34635923
2022 miR-378a negatively regulates mt-ATP6 protein abundance in mitochondria of the diabetic heart; knockout of miR-378a in a T2DM mouse model preserved mt-ATP6 and ATP synthase protein content and activity and preserved cardiac function. The lncRNA Kcnq1ot1 can bind and reduce miR-378a levels, rescuing mt-ATP6 and ATP synthase protein content, establishing a Kcnq1ot1/miR-378a/mt-ATP6 regulatory axis. miR-378a knockout mouse model (Db/Db T2DM background), lncRNA Kcnq1ot1 overexpression in HL-1 cardiomyocytes, ATP synthase activity assay, Western blot for mt-ATP6 and ATP synthase, cardiac function measurement American journal of physiology. Cell physiology Medium 35108116
2020 Truncating MT-ATP6 mutations (m.8782G>A p.Gly86* and m.8618dup p.Thr33Hisfs*32) cause impaired complex V assembly (multiple BN-PAGE bands indicating subcomplexes), reduced basal respiration and ATP synthesis by microscale oxygraphy, and increased reactive oxygen species generation in patient fibroblasts and skeletal muscle. Cybrid studies confirmed pathogenicity of the novel truncating variant. BN-PAGE of patient fibroblasts and skeletal muscle, microscale oxygraphy (respiration and ATP synthesis), ROS measurement, transmitochondrial cybrid cell lines Neurology. Genetics High 32042910

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus. Nature genetics 202 11925565
1994 Cytoplasmic transfer of the mtDNA nt 8993 T-->G (ATP6) point mutation associated with Leigh syndrome into mtDNA-less cells demonstrates cosegregation with a decrease in state III respiration and ADP/O ratio. Proceedings of the National Academy of Sciences of the United States of America 162 8078883
1995 A novel mitochondrial ATPase 6 point mutation in familial bilateral striatal necrosis. Annals of neurology 149 7668837
1992 Subacute necrotizing encephalopathy: oxidative phosphorylation defects and the ATPase 6 point mutation. Neurology 134 1436530
1993 Distinct roles of cdk2 and cdc2 in RP-A phosphorylation during the cell cycle. Journal of cell science 132 8308077
1990 Inhibition of cGMP-dependent protein kinase by (Rp)-guanosine 3',5'-monophosphorothioates. FEBS letters 126 2158906
2019 MT-ATP6 mitochondrial disease variants: Phenotypic and biochemical features analysis in 218 published cases and cohort of 14 new cases. Human mutation 101 30763462
2016 RP-MDM2-p53 Pathway: Linking Ribosomal Biogenesis and Tumor Surveillance. Trends in cancer 91 28741571
2012 Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease. Neurology 87 22933740
2020 Delineating MT-ATP6-associated disease: From isolated neuropathy to early onset neurodegeneration. Neurology. Genetics 85 32042921
2007 Biochemical phenotypes associated with the mitochondrial ATP6 gene mutations at nt8993. Biochimica et biophysica acta 85 17568559
2009 Mitochondrial DNA background modifies the bioenergetics of NARP/MILS ATP6 mutant cells. Human molecular genetics 80 19875463
1998 The molecular mechanism of B cell activation by toll-like receptor protein RP-105. The Journal of experimental medicine 75 9653087
1999 EB/RP gene family encodes tubulin binding proteins. International journal of cancer 74 10188731
2010 Hereditary spastic paraplegia-like disorder due to a mitochondrial ATP6 gene point mutation. Mitochondrion 70 20656066
2001 The typically mitochondrial DNA-encoded ATP6 subunit of the F1F0-ATPase is encoded by a nuclear gene in Chlamydomonas reinhardtii. The Journal of biological chemistry 69 11744727
2011 The RP-Mdm2-p53 pathway and tumorigenesis. Oncotarget 67 21406728
1995 (RP)-cAMPS inhibits the cAMP-dependent protein kinase by blocking the cAMP-induced conformational transition. FEBS letters 66 7498506
1994 A single homogeneous form of ATP6 protein accumulates in petunia mitochondria despite the presence of differentially edited atp6 transcripts. The Plant cell 66 7866035
1990 A chimeric gene containing the 5' portion of atp6 is associated with cytoplasmic male-sterility of rice. Molecular & general genetics : MGG 63 2148966
2006 ATP6 homoplasmic mutations inhibit and destabilize the human F1F0-ATP synthase without preventing enzyme assembly and oligomerization. The Journal of biological chemistry 61 17121862
2022 Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306. Journal of medicinal chemistry 60 35880755
2004 Diminished synthesis of subunit a (ATP6) and altered function of ATP synthase and cytochrome c oxidase due to the mtDNA 2 bp microdeletion of TA at positions 9205 and 9206. The Biochemical journal 55 15265003
1997 Cell type-specific loss of atp6 RNA editing in cytoplasmic male sterile Sorghum bicolor. Proceedings of the National Academy of Sciences of the United States of America 55 9380764
2005 Two new mutations in the MTATP6 gene associated with Leigh syndrome. Neuropediatrics 52 16217706
2013 Episodic weakness due to mitochondrial DNA MT-ATP6/8 mutations. Neurology 49 24153443
2016 A novel mutation m.8561C>G in MT-ATP6/8 causing a mitochondrial syndrome with ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic hypogonadism. Journal of neurology 48 27502083
1992 Purification and functional characterization of bovine RP-A in an in vitro SV40 DNA replication system. Chromosoma 48 1337880
1996 Alloplasmic male-sterile Brassica lines containing B. tournefortii mitochondria express an ORF 3' of the atp6 gene and a 32 kDa protein. off. Plant molecular biology 47 8980539
2003 Dancing with complement C4 and the RP-C4-CYP21-TNX (RCCX) modules of the major histocompatibility complex. Progress in nucleic acid research and molecular biology 46 14604014
2016 Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant. Nucleic acids research 43 27596602
2012 Adult-onset spinocerebellar ataxia syndromes due to MTATP6 mutations. Journal of neurology, neurosurgery, and psychiatry 43 22577227
2007 Variable phenotype including Leigh syndrome with a 9185T>C mutation in the MTATP6 gene. Neuropediatrics 42 18461509
2019 Pathogenic variants in MT-ATP6: A United Kingdom-based mitochondrial disease cohort study. Annals of neurology 41 31187502
2018 EMP18 functions in mitochondrial atp6 and cox2 transcript editing and is essential to seed development in maize. The New phytologist 41 30168136
2017 Two mutations in mitochondrial ATP6 gene of ATP synthase, related to human cancer, affect ROS, calcium homeostasis and mitochondrial permeability transition in yeast. Biochimica et biophysica acta. Molecular cell research 41 28986220
1988 Sequence analysis of the wheat mitochondrial atp6 gene reveals a fused upstream reading frame and markedly divergent N termini among plant ATP6 proteins. Gene 41 2907499
1993 The NAM1/MTF2 nuclear gene product is selectively required for the stability and/or processing of mitochondrial transcripts of the atp6 and of the mosaic, cox1 and cytb genes in Saccharomyces cerevisiae. Molecular & general genetics : MGG 38 8413192
2016 Expression of mitochondrial genes MT-ND1, MT-ND6, MT-CYB, MT-COI, MT-ATP6, and 12S/MT-RNR1 in colorectal adenopolyps. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 27333991
2010 What limits the allotopic expression of nucleus-encoded mitochondrial genes? The case of the chimeric Cox3 and Atp6 genes. Mitochondrion 37 20854934
2020 Roles of C/EBP class bZip proteins in the growth and cell competition of Rp ('Minute') mutants in Drosophila. eLife 36 31909714
2010 Online nanoflow RP-RP-MS reveals dynamics of multicomponent Ku complex in response to DNA damage. Journal of proteome research 36 20873769
1994 The NAM1 protein (NAM1p), which is selectively required for cox1, cytb and atp6 transcript processing/stabilisation, is located in the yeast mitochondrial matrix. European journal of biochemistry 36 8200349
2018 Optimized Mitochondrial Targeting of Proteins Encoded by Modified mRNAs Rescues Cells Harboring Mutations in mtATP6. Cell reports 35 29539412
2014 Expanding the clinical phenotypes of MT-ATP6 mutations. Human molecular genetics 34 24986921
2014 Novel mitochondrial mutations in the ATP6 and ATP8 genes in patients with breast cancer. Molecular medicine reports 34 25110199
2016 Disruption of the RP-MDM2-p53 pathway accelerates APC loss-induced colorectal tumorigenesis. Oncogene 32 27617574
2020 Expanding the molecular and phenotypic spectrum of truncating MT-ATP6 mutations. Neurology. Genetics 31 32042910
2003 Electroporation of isolated higher-plant mitochondria: transcripts of an introduced cox2 gene, but not an atp6 gene, are edited in organello. Molecular genetics and genomics : MGG 31 12811542
2002 Physical interaction between hepatitis C virus NS4B protein and CREB-RP/ATF6beta. Biochemical and biophysical research communications 31 12445808
2011 Combinatorial use of offline SCX and online RP-RP liquid chromatography for iTRAQ-based quantitative proteomics applications. Molecular bioSystems 30 21350782
1992 Different organization and altered transcription of the mitochondrial atp6 gene in the male-sterile cytoplasm of rapeseed (Brassica napus L.). Current genetics 29 1533177
2018 Cistanche deserticola polysaccharides protects PC12 cells against OGD/RP-induced injury. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 29710464
2008 Altered expression of 12S/MT-RNR1, MT-CO2/COX2, and MT-ATP6 mitochondrial genes in prostate cancer. The Prostate 28 18409190
1997 Effects of PTH-rP(107-111) and PTH-rP(7-34) on adult cardiomyocytes. Journal of molecular and cellular cardiology 27 9405180
2010 Phylogenetic relationships of the Gomphales based on nuc-25S-rDNA, mit-12S-rDNA, and mit-atp6-DNA combined sequences. Fungal biology 26 20943133
2024 Discovery of the Potent and Selective ATR Inhibitor Camonsertib (RP-3500). Journal of medicinal chemistry 25 38299539
2022 Manipulation of the miR-378a/mt-ATP6 regulatory axis rescues ATP synthase in the diabetic heart and offers a novel role for lncRNA Kcnq1ot1. American journal of physiology. Cell physiology 25 35108116
2019 Proteasome 19S RP and translation preinitiation complexes are secreted within exosomes upon serum starvation. Traffic (Copenhagen, Denmark) 24 31042005
2017 A novel mitochondrial ATP6 frameshift mutation causing isolated complex V deficiency, ataxia and encephalomyopathy. European journal of medical genetics 24 28412374
2005 Mitochondrial electroporation and in organello RNA editing of chimeric atp6 transcripts. Molecular genetics and genomics : MGG 24 15729585
2017 Genetic diversity of ATP8 and ATP6 genes is associated with high-altitude adaptation in yak. Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis 22 28306370
2013 How the nucleus and mitochondria communicate in energy production during stress: nuclear MtATP6, an early-stress responsive gene, regulates the mitochondrial F₁F₀-ATP synthase complex. Molecular biotechnology 22 23208548
2010 T. gondii RP promoters & knockdown reveal molecular pathways associated with proliferation and cell-cycle arrest. PloS one 22 21124925
2018 Novel insights into the functional metabolic impact of an apparent de novo m.8993T>G variant in the MT-ATP6 gene associated with maternally inherited form of Leigh Syndrome. Molecular genetics and metabolism 21 29602698
2016 Regulation of mitochondrial translation of the ATP8/ATP6 mRNA by Smt1p. Molecular biology of the cell 21 26823015
2014 Cytochrome P450 inhibitory potential and RP-HPLC standardization of trikatu--a Rasayana from Indian Ayurveda. Journal of ethnopharmacology 21 24690772
2013 Polymorphisms in the MT-ATP6 and MT-CYB genes in in vitro fertilization failure. Mitochondrial DNA 21 24102627
2012 Investigation of the Mitochondrial ATPase 6/8 and tRNA(Lys) Genes Mutations in Autism. Cell journal 21 23508290
2008 Identification and functional characterization of a novel splicing mutation in RP gene PRPF31. Biochemical and biophysical research communications 21 18177735
2018 Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6. Mitochondrion 20 29307858
2012 Nuclear expression of a mitochondrial DNA gene: mitochondrial targeting of allotopically expressed mutant ATP6 in transgenic mice. Journal of biomedicine & biotechnology 20 22778551
2003 Sequence polymorphisms within the human mitochondrial genes MTATP6, MTATP8 and MTND4. International journal of legal medicine 20 12734709
1995 Cloning of mouse RP-8 cDNA and its expression during apoptosis of lymphoid and myeloid cells. DNA and cell biology 20 7880439
1993 Evolution of the mitochondrial ATPase 6 gene in Drosophila: unusually high level of polymorphism in D. melanogaster. Genetical research 20 8365657
2022 Threshold of heteroplasmic truncating MT-ATP6 mutation in reprogramming, Notch hyperactivation and motor neuron metabolism. Human molecular genetics 18 34635923
2021 RNA pull-down confocal nanoscanning (RP-CONA) detects quercetin as pri-miR-7/HuR interaction inhibitor that decreases α-synuclein levels. Nucleic acids research 18 34107032
2020 Comparison of Sigma 1 Receptor Ligands SA4503 and PRE084 to (+)-Pentazocine in the rd10 Mouse Model of RP. Investigative ophthalmology & visual science 18 33137196
2018 Improved S-adenosylmethionine and glutathione biosynthesis by heterologous expression of an ATP6 gene in Candida utilis. Journal of basic microbiology 18 30063253
2021 Mutations in MT-ATP6 are a frequent cause of adult-onset spinocerebellar ataxia. Journal of neurology 16 34037856
2019 A novel variant m.8561C>T in the overlapping region of MT-ATP6 and MT-ATP8 in a child with early-onset severe neurological signs. Molecular genetics and metabolism reports 16 31788426
2007 Investigation on mitochondrial tRNA(Leu/Lys), NDI and ATPase 6/8 in Iranian multiple sclerosis patients. Cellular and molecular neurobiology 16 17619138
2022 MYB308-mediated transcriptional activation of plasma membrane H -ATPase 6 promotes iron uptake in citrus. Horticulture research 15 35685222
2019 Zinc finger protein RP-8, the Bombyx mori ortholog of programmed cell death 2, regulates cell proliferation. Developmental and comparative immunology 15 31730828
2015 High-altitude adaptation of Tibetan chicken from MT-COI and ATP-6 perspective. Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis 15 25693693
2007 Unusual thermal stability of RNA/[RP-PS]-DNA/RNA triplexes containing a homopurine DNA strand. Biophysical journal 15 17218459
2021 Epilepsy in MT-ATP6 - related mils/NARP: correlation of elettroclinical features with heteroplasmy. Annals of clinical and translational neurology 14 33476484
2021 Genotype-phenotype analysis of MT-ATP6-associated Leigh syndrome. Acta neurologica Scandinavica 14 34877647
2019 The pathogenic MT-ATP6 m.8851T>C mutation prevents proton movements within the n-side hydrophilic cleft of the membrane domain of ATP synthase. Biochimica et biophysica acta. Bioenergetics 14 31181185
2008 [Mutation of MTCYB and MTATP6 is associated with asthenospermia]. Zhonghua nan ke xue = National journal of andrology 14 18481423
2022 Separation of long-stranded RNAs by RP-HPLC using an octadecyl-based column with super-wide pores. Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 13 36566342
2016 LTD, RP, and Motor Learning. Cerebellum (London, England) 13 26160222
2012 Isolation and in silico functional analysis of MtATP6, a 6-kDa subunit of mitochondrial F₁F0-ATP synthase, in response to abiotic stress. Genetics and molecular research : GMR 13 23096681
2022 Clinical Heterogeneity in MT-ATP6 Pathogenic Variants: Same Genotype-Different Onset. Cells 12 35159298
2022 Ribosomal protein RPL11 haploinsufficiency causes anemia in mice via activation of the RP-MDM2-p53 pathway. The Journal of biological chemistry 12 36435197
2019 Novel Thienopyrimidine Derivative, RP-010, Induces β-Catenin Fragmentation and Is Efficacious against Prostate Cancer Cells. Cancers 12 31126091
2019 Early infantile-onset Leigh syndrome complicated with infantile spasms associated with the m.9185 T > C variant in the MT-ATP6 gene: Expanding the clinical spectrum. Brain & development 12 31500933
2014 Motor Neuron Syndrome as a New Phenotypic Manifestation of Mutation 9185T>C in Gene MTATP6. Case reports in neurological medicine 12 25548692
1999 Mutation of the mitochrondrially encoded ATPase 6 gene modeled in the ATP synthase of Escherichia coli. FEBS letters 12 10403398
1999 Nuclear genes from Tx CMS maintainer lines are unable to maintain atp6 RNA editing in any anther cell-type in the sorghum bicolor A3 cytoplasm. Current genetics 12 10447596

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