Affinage

MT-ND6

NADH-ubiquinone oxidoreductase chain 6 · UniProt P03923

Length
174 aa
Mass
18.6 kDa
Annotated
2026-04-28
94 papers in source corpus 20 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MT-ND6 encodes a core transmembrane subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase) that is essential for assembly of the enzyme's membrane arm and for coupled electron transfer and proton translocation. ND6 delineates the ubiquinone-binding cavity of Complex I without directly participating in catalysis; pathogenic missense mutations at conserved residues (e.g., M64V, M63V) alter ubiquinone reduction kinetics and inhibitor sensitivity, impair Complex I assembly and stability, reduce ATP production, and elevate reactive oxygen species, triggering downstream apoptosis and dysregulated PINK1/Parkin-dependent mitophagy (PMID:9707444, PMID:15736965, PMID:17894548, PMID:35567411, PMID:37537557). ND6 expression is regulated by the transcription factor MEF2D in dopaminergic neurons and is subject to epigenetic silencing via DNMT1-mediated mitochondrial DNA methylation, linking ND6 levels to metabolic homeostasis and insulin sensitivity (PMID:31520529, PMID:34141522). Mutations in MT-ND6 are a primary cause of Leber hereditary optic neuropathy and Leigh syndrome, with pathogenicity established through cybrid reconstitution and allotopic rescue experiments (PMID:7488023, PMID:14595656, PMID:37537557).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 Medium

    Establishing that ND6 mutations cause Complex I enzymatic deficiency in patients resolved the question of whether the T14484C LHON mutation directly impairs oxidative phosphorylation.

    Evidence Complex I electron transfer activity and ATP synthesis measured in leukocytes from LHON patients carrying the ND6 M64V mutation

    PMID:7488023

    Open questions at the time
    • Activity measured in a single tissue type (leukocytes)
    • Assembly state of Complex I not assessed
    • No cybrid confirmation to exclude nuclear background effects
  2. 1998 High

    Demonstrating that complete loss of ND6 abolishes membrane-arm assembly and nearly eliminates Complex I activity established ND6 as an essential structural subunit required for Complex I biogenesis.

    Evidence Near-homoplasmic ND6 frameshift mutation transferred to rho0 cells via cybrid analysis; digitonin-permeabilized cell respiration and NADH:Q1 oxidoreductase activity assays

    PMID:9707444

    Open questions at the time
    • Mechanism by which ND6 absence prevents membrane-arm assembly not determined
    • Whether ND6 acts as a scaffold or chaperone during assembly unclear
  3. 1999 Medium

    The finding that the M64V mutation increases sensitivity to ubiquinol-site inhibitors without reducing overall Complex I activity suggested ND6 participates in ubiquinone/ubiquinol interaction rather than electron transfer per se.

    Evidence Spectrophotometric Complex I assays with inhibitor titrations in patient platelet submitochondrial particles; comparative sequence analysis with cytochrome b

    PMID:10072046

    Open questions at the time
    • Structural basis of ubiquinol-site interaction inferred from sequence homology only
    • No direct binding assay for ubiquinone
  4. 2003 High

    Showing that the M63V mutation impairs Complex I assembly in a heteroplasmy-dependent manner extended the functional role of ND6 beyond the M64V LHON allele to a second conserved residue causing Leigh syndrome.

    Evidence Blue Native gel electrophoresis and Complex I activity assays in cybrid cells correlated with heteroplasmy levels

    PMID:14520668 PMID:14595656

    Open questions at the time
    • Structural difference between M63V and M64V assembly defects not resolved
    • Threshold heteroplasmy for clinical disease not precisely defined
  5. 2005 High

    Systematic mutagenesis of the ND6 homolog NuoJ in E. coli demonstrated that ND6 is critical for proton translocation and energy coupling but dispensable for NADH dehydrogenase activity, separating its role in electron input from proton pumping.

    Evidence Targeted chromosomal mutagenesis in E. coli; coupled electron transfer, proton translocation, and membrane potential assays

    PMID:15736965

    Open questions at the time
    • Bacterial system may not fully recapitulate mammalian Complex I coupling mechanism
    • Direct proton channel mapping through ND6 not achieved
  6. 2005 Medium

    ROS overproduction was identified as a direct consequence of ND6 mutations, linking Complex I deficiency to oxidative damage of lipids and mtDNA as a pathogenic mechanism.

    Evidence Homoplasmic T14487C cybrid cells; ROS, lipid oxidation, and mtDNA oxidation measurements

    PMID:16337195

    Open questions at the time
    • Whether ROS is a primary driver of pathology or secondary consequence not distinguished
    • Antioxidant rescue experiments not performed
  7. 2006 High

    Discovery that a nuclear suppressor can restore Complex I assembly in ND6-null cells revealed that the requirement for ND6 in assembly can be bypassed, implying nuclear-mitochondrial compensatory mechanisms.

    Evidence Galactose selection for suppressor clones; reciprocal mtDNA transfer demonstrating nuclear origin; Complex I assembly and respiratory activity assays

    PMID:16428459

    Open questions at the time
    • Identity of the nuclear suppressor gene not determined
    • Mechanism of suppression (bypass vs. substitute) unknown
  8. 2008 High

    Mapping LHON-equivalent mutations onto E. coli NDH-1 established that ND6 delineates the ubiquinone-binding cavity and that disease-causing residues specifically alter ubiquinone reduction kinetics and binding affinity.

    Evidence Systematic mutagenesis of NuoJ in E. coli; decylubiquinone reductase activity and inhibitor sensitivity assays

    PMID:17894548

    Open questions at the time
    • No high-resolution structure of ubiquinone bound in the ND6 cavity at this time
    • Precise contacts between ND6 and ubiquinone not mapped
  9. 2019 Medium

    Identifying MEF2D as a transcriptional regulator of ND6 in dopaminergic neurons linked mitochondrial Complex I maintenance to a nuclear transcription factor pathway relevant to Parkinson-like neurodegeneration.

    Evidence MEF2D-blocking plasmid in SH-SY5Y cells and MPTP mouse model; Complex I activity, membrane potential, and ND6 protein measurements

    PMID:31520529

    Open questions at the time
    • Direct MEF2D binding to mt-ND6 regulatory region not demonstrated
    • Mechanism of nuclear MEF2D regulating a mitochondrial-encoded gene unclear
  10. 2021 Medium

    Demonstrating that DNMT1-mediated methylation of ND6 reduces its transcription and causes mitochondrial dysfunction and insulin resistance revealed an epigenetic regulatory layer controlling ND6 expression with systemic metabolic consequences.

    Evidence mtDNA methylation sequencing; hepatic ND6 knockdown and Dnmt1 overexpression in mice and cell lines; mitochondrial function and insulin resistance assays

    PMID:34141522

    Open questions at the time
    • Specificity of DNMT1 methylation for ND6 versus other mt-encoded genes not fully resolved
    • Whether mt-DNA methylation is a physiological regulatory mechanism or a stress response debated
  11. 2022 High

    Comprehensive characterization of the m.14484T>C mutation in cybrids unified the mechanistic picture: ND6 M64V disrupts interactions with Y59, ND4L, and ND1, causing assembly defects, respiratory failure, elevated ROS, apoptosis activation, and impaired PINK1/Parkin mitophagy.

    Evidence Mutant cybrids; Blue Native gel electrophoresis; extracellular flux analysis; apoptosis and mitophagy protein analysis; structural analysis of Complex I

    PMID:35567411

    Open questions at the time
    • Whether mitophagy impairment is a direct consequence of ND6 mutation or secondary to energetic collapse
    • Patient tissue validation of mitophagy defect not performed
  12. 2023 High

    Allotopic rescue of ND6 function in mutant cybrids provided proof-of-concept that re-expression of wild-type ND6 can reverse Complex I deficiency, ROS elevation, apoptosis, and mitophagy dysregulation, establishing a potential gene therapy framework.

    Evidence Codon-optimized ND6 with COX8 targeting sequence stably transfected into m.14484T>C cybrids; assembly, bioenergetic, ROS, apoptosis, and mitophagy readouts

    PMID:37537557

    Open questions at the time
    • Only ~20-23% restoration of Complex I activity achieved
    • In vivo delivery and efficacy of allotopic ND6 not tested
    • Whether partial rescue is sufficient for therapeutic benefit unknown
  13. 2025 Medium

    An ND6 mutation that specifically abrogates reverse electron transport while preserving forward NADH dehydrogenase activity showed that Complex I deactivation renders carotid body glomus cells insensitive to acute hypoxia, implicating ND6 conformation in oxygen sensing.

    Evidence Mouse model with ND6 point mutation; electrophysiological recording of glomus cell hypoxia responses; Complex I forward and reverse activity assays

    PMID:39981615

    Open questions at the time
    • Whether this ND6-dependent deactivation mechanism operates in other oxygen-sensing tissues unknown
    • Structural basis of active-to-deactive transition involving ND6 not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the nuclear suppressor that bypasses ND6 requirement for Complex I assembly remains unknown, and whether ND6's role in ubiquinone binding can be structurally resolved at atomic detail in the human enzyme with bound substrate is an open question.
  • Nuclear suppressor gene identity unknown
  • No human Complex I structure with ubiquinone bound in the ND6-delineated cavity
  • Mechanism by which MEF2D regulates a mitochondrial-encoded gene remains unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0016491 oxidoreductase activity 3 GO:0005215 transporter activity 1
Localization
GO:0005739 mitochondrion 7
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1643685 Disease 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-5357801 Programmed Cell Death 2
Partners
DNMT1MEF2DND1ND4LND5PINK1PRKN
Complex memberships
Complex I (NADH:ubiquinone oxidoreductase)

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 ND6 is essential for assembly of the membrane arm of mitochondrial Complex I and for its respiratory function; a frameshift mutation abolishing ND6 expression causes loss of assembly of all mtDNA-encoded Complex I subunits, ~90% reduction in malate/glutamate-dependent respiration, and ~99% reduction in NADH:Q1 oxidoreductase activity. Cell line with near-homoplasmic ND6 frameshift mutation; mitochondrial transfer to rho0 cells (cybrid analysis); biosynthetic and functional assays including digitonin-permeabilized cell respiration and NADH:Q1 oxidoreductase activity measurement; galactose growth assay The EMBO journal High 9707444
1995 The ND6 T14484C (M64V) LHON mutation reduces Complex I electron transfer activity to ~35% of control in patient leukocytes and decreases Complex I-linked ATP synthesis by ~20%, demonstrating that all three primary LHON mtDNA mutations cause Complex I deficiency. Biochemical measurement of Complex I electron transfer activity and Complex I-linked ATP synthesis in leukocytes from LHON patients Biochemical and biophysical research communications Medium 7488023
1999 The ND6 T14484C (M64V) LHON mutation does not reduce Complex I specific activity but significantly increases sensitivity of Complex I to ubiquinol-site inhibitors myxothiazol and nonylbenzoquinol, suggesting the mutation affects the ubiquinol product interaction site of Complex I; sequence analysis shows ND6 residue 64 lies in a region with local similarity to cytochrome b regions interacting with ubiquinone/ubiquinol in Complex III. Spectrophotometric measurement of Complex I specific activity and inhibitor sensitivity in platelet submitochondrial particles; comparative amino acid sequence analysis Annals of neurology Medium 10072046
2003 The ND6 T14487C (M63V) mutation causes impaired Complex I assembly and/or stability, as demonstrated by altered mobility and decreased levels of fully assembled Complex I in patient fibroblasts and cybrid cell lines, with Complex I deficiency correlating with mutant heteroplasmy levels. Cybrid cell lines; Blue Native gel electrophoresis to assess Complex I assembly; biochemical Complex I activity assays correlated with heteroplasmy levels Annals of neurology High 14520668 14595656
2005 In E. coli NDH-1, the ND6 homolog NuoJ (particularly Val-65 in the most conserved transmembrane segment) is important for energy transduction (proton translocation) but not for enzyme assembly or NADH-ferricyanide reductase activity; mutations at this position significantly reduce coupled electron-transfer activity, membrane potential, and proton translocation. Chromosomal DNA manipulation in E. coli; Blue-native gel electrophoresis; deamino-NADH:ferricyanide reductase assay; coupled electron-transfer assays; membrane potential measurements; proton translocation assays Biochemistry High 15736965
2008 LHON mutations in ND6 affect ubiquinone reduction kinetics in E. coli NDH-1; the NuoJ-M64V equivalent (common LHON mutation) mildly reduces decylubiquinone reductase activity and lowers affinity for ubiquinone, while nearby mutations (Y59F, V65G, M72V) severely impair ubiquinone reduction. ND6 delineates the ubiquinone substrate binding cavity but does not directly participate in catalysis. E. coli NDH-1 mutagenesis; deamino-NADH:HAR reductase assay (assembly control); decylubiquinone reductase activity assay; growth on malate minimal medium; inhibitor sensitivity assays The Biochemical journal High 17894548
2005 The ND6 T14487C mutation in transmitochondrial cybrid cells causes Complex I deficiency and overproduction of reactive oxygen species (ROS), leading to increased oxidation of lipids and mtDNA, without modification of antioxidant enzyme activities. Transmitochondrial cybrid cells with homoplasmic T14487C mutation; ROS measurement; lipid oxidation assays; mtDNA oxidation assays; antioxidant enzyme activity measurements FEBS letters Medium 16337195
2006 A nucleus-encoded suppressor can compensate for the absence of ND6 protein: a galactose-resistant clone (4AR) derived from ND6-deficient cells showed recovery of Complex I subunit assembly, respiratory activity, and mitochondrial membrane potential despite continued absence of ND6 protein; the suppression was shown to be nuclear in origin by mtDNA transfer experiments and could also suppress ND5 deficiency. Galactose selection for suppressors; mtDNA transfer to new nuclear background (cybrid analysis); Complex I assembly assays; respiratory activity measurements; mitochondrial membrane potential assays Molecular and cellular biology High 16428459
2015 ND6 nonsense and missense mutations in human lung adenocarcinoma cells promote cell migration and invasion through NADH dehydrogenase deficiency-induced ROS overproduction, with activation of pAKT and pERK1/2 signaling pathways. Cytoplasmic hybrid (cybrid) cells constructed with mutant mitochondria from patient tissue and mtDNA-depleted A549 nuclear background; wound healing and Matrigel transwell invasion assays; spectrophotometric NADH dehydrogenase activity; flow cytometry for ROS; western blotting for pAKT and pERK1/2; rotenone inhibitor experiments BMC cancer Medium 25934296
2004 A T14634C mutation in the ND6 gene in hypoxia-sensitive glioma cells alters the predicted structure and orientation of ND6 transmembrane helices (without abolishing protein expression) and is associated with increased resistance to rotenone and adriamycin, suggesting that ND6 transmembrane structure influences Complex I function in oxygen-sensing. Mitochondrial genome sequencing; rotenone and adriamycin resistance assays; homology-based 3D structural modeling of wild-type and mutant ND6 Molecular cancer Low 15248896
2021 Hypermethylation of the ND6 gene by mitochondrially-translocated DNMT1 (promoted by free fatty acids via AMPK activation) decreases ND6 transcript levels, impairs mitochondrial function, and causes systemic insulin resistance; hepatic knockdown of ND6 or overexpression of Dnmt1 similarly impaired mitochondrial function. mtDNA methylation sequencing in mice; hepatic ND6 knockdown (in vivo and in vitro); Dnmt1 overexpression; measurement of mitochondrial function; AMPK activation studies; insulin resistance assays Advanced science Medium 34141522
2019 ND6 expression in mitochondria is regulated by the transcription factor MEF2D; in dopaminergic neurons, the MEF2D-ND6 pathway is critical for maintaining mitochondrial Complex I assembly and activity, and its disruption underlies MPTP/MPP+-induced neurodegeneration. MPP+-injured SH-SY5Y cell model and MPTP mouse model; salidroside treatment; MEF2D-blocking plasmid (Mt2Ddn) transfection; measurement of Complex I activity, mitochondrial membrane potential, MEF2D and ND6 protein expression; behavioral testing Journal of neurochemistry Medium 31520529
2022 The LHON-linked ND6 m.14484T>C (M64V) mutation causes pleiotropic effects including: decreased Complex I assembly and activity, respiratory deficiency, reduced ATP production and mitochondrial membrane potential, increased ROS, promoted apoptosis (via cytochrome c release, elevated BAX/caspases, reduced Bcl-xL), and impaired PINK1/Parkin-dependent mitophagy; structural analysis revealed M64 interacts with Y59 of ND6 and neighboring ND4L and ND1 residues. Mutant cybrids bearing m.14484T>C; Blue Native gel electrophoresis for Complex I assembly; extracellular flux analysis; flow cytometry (ROS, apoptosis); TUNEL assay; western blotting for apoptotic and mitophagy proteins; structural analysis of Complex I Human molecular genetics High 35567411
2023 Allotopic expression of a nucleus-optimized ND6 transgene (with non-universal codons replaced and mitochondrial targeting sequence added) in cybrid cells carrying the m.14484T>C mutation restored Complex I assembly and activity by 20-23%, increased mitochondrial ATP and membrane potential, reduced ROS, inhibited apoptosis, and restored impaired mitophagy. Allotopic expression vector with codon-optimized ND6 fused to COX8 mitochondrial targeting sequence; stable transfection into mutant cybrids; Blue Native gel electrophoresis; extracellular flux analysis; flow cytometry for ROS, apoptosis; TUNEL; immunofluorescence for mitophagy markers Journal of biomedical science High 37537557
2019 The m.4401A>G mutation at a spacer adjacent to mitochondrial tRNA genes causes aberrant processing of ND6 mRNA (part of the light-strand transcript), leading to decreased ND6 levels and contributing to mitochondrial translation impairment, respiratory deficiency, reduced membrane potential, increased ROS, and altered angiogenesis in endothelial cell cybrids. In vitro processing experiment with RNase P; cybrid cell lines from human umbilical vein endothelial cells; northern blotting for light-strand transcripts including ND6; measurement of membrane potential, ROS, ATP; wound healing and tube formation assays Nucleic acids research Medium 31504769
2025 A hepatocellular carcinoma-associated ND6 deletion causing a truncated protein (ΔND6, missing 50% of C-terminus) negatively affects Complex I stability and functionality, as shown by biochemical analysis and molecular dynamics simulations confirming conformational rearrangements. mtDNA sequencing of tumor tissue; expression of truncated ND6 in cells; biochemical Complex I activity assays; molecular dynamics simulations Scientific reports Medium 40157968
2025 In carotid body glomus cells, mitochondrial Complex I function (but not reverse electron transport, RET) is necessary for acute hypoxia sensing; mice with an ND6 mutation that maintains normal NADH dehydrogenase activity but cannot catalyze RET showed that the ND6 mutation increases propensity of Complex I to deactivate, and glomus cells with deactivated Complex I are insensitive to acute hypoxia. Mouse model with ND6 point mutation abrogating RET; electrophysiological recording of glomus cell hypoxia responses; Complex I activity assays; measurement of NADH and H2O2 in hypoxia FEBS letters Medium 39981615
2024 In a mouse model of Leber hereditary optic neuropathy, Nd6-deficient retinal ganglion cell axons exhibit mitochondrial hypertrophy (in contrast to Opa1 model which shows fragmentation), suggesting an adaptive response to altered energy metabolism that is detectable before neuronal loss. Pre-symptomatic hereditary optic neuropathy mouse models (Opa1 and Nd6 deficiency); mitochondrial distribution and ultrastructure analysis in retina and longitudinal optic nerve sections; mitophagy assessment Brain communications Medium 39659974
2020 miR-217 inhibits ND6 expression in a MEF2D-dependent manner; overexpression of MEF2D reverses OGD-induced downregulation of ND6 and reduces neuronal apoptosis and ROS generation, placing MEF2D upstream of ND6 in a pathway relevant to cerebral ischemic injury. OGD cell model; miR-217 overexpression/inhibition; MEF2D overexpression plasmid; ND6 protein measurement; ROS measurement; apoptosis assays; in vivo MEF2D overexpression in cerebral ischemia model Brain research Medium 32311345

Source papers

Stage 0 corpus · 94 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. Biochemical and biophysical research communications 301 1417830
1998 The mtDNA-encoded ND6 subunit of mitochondrial NADH dehydrogenase is essential for the assembly of the membrane arm and the respiratory function of the enzyme. The EMBO journal 177 9707444
2001 The mitochondrial ND6 gene is a hot spot for mutations that cause Leber's hereditary optic neuropathy. Brain : a journal of neurology 147 11133798
1999 Biochemical features of mtDNA 14484 (ND6/M64V) point mutation associated with Leber's hereditary optic neuropathy. Annals of neurology 107 10072046
2003 Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene. Annals of neurology 91 14595656
2003 Evaluating placental inter-ordinal phylogenies with novel sequences including RAG1, gamma-fibrinogen, ND6, and mt-tRNA, plus MCMC-driven nucleotide, amino acid, and codon models. Molecular phylogenetics and evolution 76 12878459
2004 Complete nucleotide sequence and organization of the naphthalene catabolic plasmid pND6-1 from Pseudomonas sp. strain ND6. Gene 68 15246534
2015 Nonsense and missense mutation of mitochondrial ND6 gene promotes cell migration and invasion in human lung adenocarcinoma. BMC cancer 60 25934296
2004 Mutation in mitochondrial complex I ND6 subunit is associated with defective response to hypoxia in human glioma cells. Molecular cancer 55 15248896
2003 Bilateral striatal necrosis associated with a novel mutation in the mitochondrial ND6 gene. Annals of neurology 54 14520668
2005 Characterization of the membrane domain subunit NuoJ (ND6) of the NADH-quinone oxidoreductase from Escherichia coli by chromosomal DNA manipulation. Biochemistry 53 15736965
2018 Hypomethylation of mitochondrial D-loop and ND6 with increased mitochondrial DNA copy number in the arsenic-exposed population. Toxicology 51 29940200
1997 Mutation analysis of the ND6 gene in patients with Lebers hereditary optic neuropathy. Biochemical and biophysical research communications 49 9177303
2014 Frequency and spectrum of mitochondrial ND6 mutations in 1218 Han Chinese subjects with Leber's hereditary optic neuropathy. Investigative ophthalmology & visual science 45 24398099
2010 ND6 gene "lost" and found: evolution of mitochondrial gene rearrangement in Antarctic notothenioids. Molecular biology and evolution 43 20106908
2021 Hypermethylation of Hepatic Mitochondrial ND6 Provokes Systemic Insulin Resistance. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 40 34141522
2018 Targeted cleavage of nad6 mRNA induced by a modified pentatricopeptide repeat protein in plant mitochondria. Communications biology 38 30320233
2009 Leber's hereditary optic neuropathy is associated with mitochondrial ND6 T14502C mutation. Biochemical and biophysical research communications 38 19732751
2002 Mitochondrial DNA nucleotide changes C14482G and C14482A in the ND6 gene are pathogenic for Leber's hereditary optic neuropathy. Annals of neurology 38 12112086
2010 Adaptive evolution of the mitochondrial ND6 gene in the domestic horse. Genetics and molecular research : GMR 37 20198570
1995 The mitochondrial DNA mutation ND6*14,484C associated with leber hereditary optic neuropathy, leads to deficiency of complex I of the respiratory chain. Biochemical and biophysical research communications 37 7488023
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 36 27333991
1998 Leber's Hereditary Optic Neuropathy (LHON) with 14484/ND6 mutation in a North African patient. Journal of the neurological sciences 35 9849804
2008 Leber hereditary optic neuropathy mutations in the ND6 subunit of mitochondrial complex I affect ubiquinone reduction kinetics in a bacterial model of the enzyme. The Biochemical journal 34 17894548
2008 T14484C and T14502C in the mitochondrial ND6 gene are associated with Leber's hereditary optic neuropathy in a Chinese family. Mitochondrion 30 18440284
2007 Antarctic fish mitochondrial genomes lack ND6 gene. Journal of molecular evolution 30 17955154
2010 Mitochondrial ND6 T14502C variant may modulate the phenotypic expression of LHON-associated G11778A mutation in four Chinese families. Biochemical and biophysical research communications 29 20691156
2006 Nuclear suppression of mitochondrial defects in cells without the ND6 subunit. Molecular and cellular biology 29 16428459
2005 Free radicals-mediated damage in transmitochondrial cells harboring the T14487C mutation in the ND6 gene of mtDNA. FEBS letters 27 16337195
2002 Confirmation of the 14568 mutation in the mitochondrial ND6 gene as causative in Leber's hereditary optic neuropathy. Ophthalmic genetics 27 12324878
1999 Leber's hereditary optic neuropathy: clinical and molecular genetic findings in a patient with a new mutation in the ND6 gene. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 26 10447650
2013 Mitochondrial haplotypes may modulate the phenotypic manifestation of the LHON-associated m.14484T>C (MT-ND6) mutation in Chinese families. Mitochondrion 25 23665487
2005 A novel mtDNA ND6 gene mutation associated with LHON in a Caucasian family. Biochemical and biophysical research communications 25 15922297
2019 Hypertension-associated mitochondrial DNA 4401A>G mutation caused the aberrant processing of tRNAMet, all 8 tRNAs and ND6 mRNA in the light-strand transcript. Nucleic acids research 24 31504769
2012 Mitochondrial function in Antarctic nototheniids with ND6 translocation. PloS one 24 22363756
2022 Leber's hereditary optic neuropathy-associated ND6 14484T > C mutation caused pleiotropic effects on the complex I, RNA homeostasis, apoptosis and mitophagy. Human molecular genetics 23 35567411
2014 New MT-ND6 and NDUFA1 mutations in mitochondrial respiratory chain disorders. Annals of clinical and translational neurology 22 25356405
2011 Physiological role of the novel salicylaldehyde dehydrogenase NahV in mineralization of naphthalene by Pseudomonas putida ND6. Microbiological research 22 21376550
2019 Salidroside protects dopaminergic neurons by regulating the mitochondrial MEF2D-ND6 pathway in the MPTP/MPP+ -induced model of Parkinson's disease. Journal of neurochemistry 20 31520529
2013 Severe infantile leigh syndrome associated with a rare mitochondrial ND6 mutation, m.14487T>C. American journal of medical genetics. Part A 20 23813926
2007 The coexistence of mitochondrial ND6 T14484C and 12S rRNA A1555G mutations in a Chinese family with Leber's hereditary optic neuropathy and hearing loss. Biochemical and biophysical research communications 20 17452034
2005 Overexpression, purification and characterization of a new salicylate hydroxylase from naphthalene-degrading Pseudomonas sp. strain ND6. Microbiological research 20 16035243
2021 Impact of Mitochondrial Genetic Variants in ND1, ND2, ND5, and ND6 Genes on Sperm Motility and Intracytoplasmic Sperm Injection (ICSI) Outcomes. Reproductive sciences (Thousand Oaks, Calif.) 19 33475980
2012 Complete genome sequence of the naphthalene-degrading Pseudomonas putida strain ND6. Journal of bacteriology 19 22933774
2020 miR-217-regulated MEF2D-HDAC5/ND6 signaling pathway participates in the oxidative stress and inflammatory response after cerebral ischemia. Brain research 18 32311345
2019 Leber hereditary optic neuropathy plus dystonia, and transverse myelitis due to double mutations in MT-ND4 and MT-ND6. Journal of neurology 18 31776719
1993 The nad6 gene and the exon d of nad1 are co-transcribed in wheat mitochondria. Current genetics 18 7507801
2009 Low penetrance of Leber's hereditary optic neuropathy in ten Han Chinese families carrying the ND6 T11484C mutation. Biochimica et biophysica acta 17 19733221
2008 Two mtDNA mutations 14487T>C (M63V, ND6) and 12297T>C (tRNA Leu) in a Leigh syndrome family. Molecular genetics and metabolism 17 19062322
2010 Juvenile Leigh syndrome, optic atrophy, ataxia, dystonia, and epilepsy due to T14487C mutation in the mtDNA-ND6 gene: a mitochondrial syndrome presenting from birth to adolescence. Journal of child neurology 16 21196529
2006 Leber's hereditary optic neuropathy is associated with the mitochondrial ND6 T14484C mutation in three Chinese families. Biochemical and biophysical research communications 16 16806060
2002 A mutational hot spot in the mitochondrial ND6 gene in patients with Leber's hereditary optic neuropathy. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 15 11931086
2023 Optimized allotopic expression of mitochondrial ND6 transgene restored complex I and apoptosis deficiencies caused by LHON-linked ND6 14484T > C mutation. Journal of biomedical science 14 37537557
2021 A high mutation load of m.14597A>G in MT-ND6 causes Leigh syndrome. Scientific reports 14 34045482
1989 RNAs containing mitochondrial ND6 and COI sequences present an abnormal structure in chemically induced rat hepatomas. Nucleic acids research 14 2548155
1999 Dynamically heterogenous partitions and phylogenetic inference: an evaluation of analytical strategies with cytochrome b and ND6 gene sequences in cranes. Molecular phylogenetics and evolution 13 10603258
2004 Catechol 2,3-dioxygenase from Pseudomonas sp. strain ND6: gene sequence and enzyme characterization. Bioscience, biotechnology, and biochemistry 12 15322368
2022 Mitochondrial Diabetes is Associated with tRNALeu(UUR) A3243G and ND6 T14502C Mutations. Diabetes, metabolic syndrome and obesity : targets and therapy 11 35685248
2004 [A patient with bilateral lesion in the striatum and slowly progressive dystonia secondary to T14487C mutation in the ND6 gene of complex I of the mitochondrial respiratory chain]. Revista de neurologia 11 15625630
1993 Characterization of the Brassica campestris mitochondrial gene for subunit six of NADH dehydrogenase: nad6 is present in the mitochondrion of a wide range of flowering plants. Current genetics 11 8431956
2001 Sources of incongruence among mammalian mitochondrial sequences: COII, COIII, and ND6 genes are main contributors. Molecular phylogenetics and evolution 10 11603936
2021 Nano-CuO causes cell damage through activation of dose-dependent autophagy and mitochondrial lncCyt b-AS/ND5-AS/ND6-AS in SH-SY5Y cells. Toxicology mechanisms and methods 9 34353230
2011 A phylogeny of the temperate seabasses (Moronidae) characterized by a translocation of the mt-nd6 gene. Journal of fish biology 9 22220893
2020 Systematic analysis of a mitochondrial disease-causing ND6 mutation in mitochondrial deficiency. Molecular genetics & genomic medicine 8 32162843
2015 Leber's Hereditary Optic Neuropathy is Associated with Compound Primary Mutations of Mitochondrial ND1 m.3635G > A and ND6 m.14502 T > C. Ophthalmic genetics 8 24417559
2012 Complete nucleotide sequence of plasmid pND6-2 from Pseudomonas putida ND6 and characterization of conjugative genes. Gene 8 23046581
2011 Exploitation of mitochondrial nad6 as a complementary marker for studying population variability in Lepidoptera. Genetics and molecular biology 8 22215980
1992 The mitochondrial NADH dehydrogenase subunit 6 (ND6) gene in Murres: relevance to phylogenetic and population studies among birds. Genome 8 1473724
2016 A De Novo Mutation in MTND6 Causes Generalized Dystonia in 2 Unrelated Children. Child neurology open 7 28503604
2021 Progressive myoclonic epilepsy due to rare mitochondrial ND6 mutation, m.14487T>C. BMJ neurology open 6 34223155
2020 Correlation between sperm mitochondrial ND5 and ND6 gene variations and total fertilisation failure. Archives of medical science : AMS 6 32399119
2023 Genetic Diversity Analysis and Breeding of Geese Based on the Mitochondrial ND6 Gene. Genes 4 37628656
2021 Function and Molecular Ecology Significance of Two Catechol-Degrading Gene Clusters in Pseudomonas putida ND6. Journal of microbiology and biotechnology 4 33323670
2021 Mild Leber hereditary optic neuropathy (LHON) in a Western European family due to the rare Asian m.14502T>C variant in the MT-ND6 gene. Ophthalmic genetics 4 33858285
2020 A novel mitochondrial m.14430A>G (MT-ND6, p.W82R) variant causes complex I deficiency and mitochondrial Leigh syndrome. Clinical chemistry and laboratory medicine 4 32432562
2014 Electrochemical detection of the MT-ND6 gene and its enzymatic digestion: application in human genomic sample. Analytical biochemistry 4 24650582
1995 Organisation of the mitochondrial genome of Trichophyton rubrum. DNA sequence analysis of the ND4 gene, the ATPase subunit-6 gene, the ribosomal RNA small-subunit gene, the ND6 gene, the COXIII gene, the ATPase subunit-8 gene and six tRNA genes that correspond respectively to the tyrosine, lysine, glutamine, asparagine, isoleucine and tryptophan isoacceptors. Current genetics 4 8593686
1993 Occurrence and transcription of genes for nad1, nad3, nad4L, and nad6, coding for NADH dehydrogenase subunits 1, 3, 4L, and 6, in liverwort mitochondria. Current genetics 4 7916672
2025 Characterization of a new mutation of mitochondrial ND6 gene in hepatocellular carcinoma and its effects on respiratory complex I. Scientific reports 3 40157968
2022 Mesenchymal stem cells improve redox homeostasis and mitochondrial respiration in fibroblast cell lines with pathogenic MT-ND3 and MT-ND6 variants. Stem cell research & therapy 3 35715829
2025 Computer-aided design of short peptide ligands targeting N-formyl peptide MT-ND6: potential application in treating severe inflammatory diseases. Journal of materials chemistry. B 2 40237035
2024 A novel mitochondrial DNA variant in MT-ND6: m.14430A>C p.(Trp82Gly) identified in a patient with Leigh syndrome and complex I deficiency. Molecular genetics and metabolism reports 2 38571879
2024 Major depressive disorder is associated with mitochondrial ND6 T14502C mutation in two Han Chinese families. World journal of psychiatry 2 39564165
2024 Opa1 and MT-Nd6 mutations induce early mitochondrial changes in the retina and prelaminar optic nerve of hereditary optic neuropathy mouse models. Brain communications 2 39659974
2025 The maize mTERF18 regulates transcriptional termination of the mitochondrial nad6 gene and is essential for kernel development. Journal of genetics and genomics = Yi chuan xue bao 1 39798667
2025 Acute oxygen sensing by arterial chemoreceptors with a mutant mitochondrial complex I ND6 subunit lacking reverse electron transport. FEBS letters 1 39981615
2022 Two Microsatellite Types Within NAD6 Gene Help to Distinguish Populations and Infer the Migratory Route of the Invasive Fall Armyworm, Spodoptera frugiperda, (Lepidoptera, Noctuidae) in China. Journal of economic entomology 1 35899806
2021 Measuring Membrane Lipid Turnover with the pH-sensitive Fluorescent Lipid Analog ND6. Journal of visualized experiments : JoVE 1 34398155
2009 Mapping of 5' and 3'-ends of sunflower mitochondrial nad6 mRNAs reveals a very complex transcription pattern which includes primary transcripts lacking 5'-UTR. Biochimie 1 19401212
2007 [Cloning and expression of catA gene from Pseudomonas putida ND6 and study on the catechol cleavage pathway]. Wei sheng wu xue bao = Acta microbiologica Sinica 1 17672292
2003 Lupin nad9 and nad6 genes and their expression: 5' termini of the nad9 gene transcripts differentiate lupin species. Gene 1 14557072
2024 Leber Hereditary Optic Neuropathy With Significant Visual Recovery: An MT-ND6 Mutation in a Malay Patient. Cureus 0 39525159
2023 Maternally inherited non-syndromic hearing loss is linked with a novel mitochondrial ND6 gene mutation. Irish journal of medical science 0 37561388
2003 [Polymorphism of the gene for subunit 6 of the NADh dehydrogenase complex (ND6) in ethnic russian population in Russia]. Molekuliarnaia biologiia 0 12942631