Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene nad4, encoding subunit four of the mitochondrial NADH dehydrogenase complex I, has been isolated and characterized from turnip, Brassica campestris. The 8 kb turnip nad4 gene contains four exons, which potentially encode a NAD4 polypeptide of 495 amino acids, and three large group II introns. Northern analysis identifies an abundant 2 kb transcript that most likely serves as the nad4 mRNA, while several larger transcripts (putative splicing intermediates) are also detected. Analysis of the nad4 locus in three distantly related dicotyledons indicates that introns 2 and 3 are optional. Mung bean has the same nad4 organization as turnip, whereas spinach nad4 contains introns 1 and 3, and lettuce nad4 has intron 1 only. We infer that all three group II introns were present in the nad4 gene of an angiosperm common ancestor and have persisted in certain lineages for over 200 million years, with two of the introns having been lost in other lineages.
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PMID:Variable intron content of the NADH dehydrogenase subunit 4 gene of plant mitochondria. 152 69

Chlamydomonas reinhardtii mitochondrial (mt)DNA was digested with ClaI + HpaI and shotgun cloned into the M13mp19 vector cleaved with AccI + SmaI. One of the recombinant clones, with a 1.8-kb DNA insert, was completely sequenced using the dideoxy chain-termination method. Besides containing part of the cytochrome b (COB)-encoding gene (cob), this DNA fragment encodes subunit 4 of NADH dehydrogenase (NAD4). The deduced amino acid sequence and hydrophilicity plot indicate that NAD4 is highly hydrophobic. The nad4 gene shows a unique preference for certain codons which are also found in other C. reinhardtii mt proteins. Both the genes encoding NAD4 and COB are shown to be transcriptionally active by Northern hybridization. These closely linked genes suggest that RNA-processing events found in vertebrate mt are present in Chlamydomonas mt as well.
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PMID:Nucleotide sequence of cloned nad4 (urf4) gene from Chlamydomonas reinhardtii mitochondrial DNA. 262 73

Comparison between the sequence of the gene coding for the wheat mitochondrial NADH dehydrogenase subunit IV (nad4) and the cDNA sequence obtained by reverse transcription, using total wheat mtRNA as template, has shown the presence of a uridine residue, not encoded by the genomic sequence, at the exon2-exon3 junction of the spliced transcript. This U creates a non-encoded CUG leucine codon which is essential for maintaining the reading frame, as shown by the conservation of the amino acid sequence of the NAD4 protein in various species. The addition of a U or the specific post-transcriptional conversion of a C to a U could explain this phenomenon.
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PMID:RNA editing at a splicing site of NADH dehydrogenase subunit IV gene transcript in wheat mitochondria. 268 23

By using the spinach chloroplast atpE gene (epsilon-subunit coding gene) as a probe we have isolated, from a soybean mitochondrial DNA library, a sequence containing a 405 base-pairs (bp) open-reading frame (ORF). This ORF, which is unique in the soybean mitochondrial genome, is probably part of an exon of the gene coding for subunit IV of the NADH dehydrogenase complex. The predicted protein shows 42% sequence similarity with the C-terminal region the Aspergillus nidulans NAD4 protein. The gene is split by a class II intron which is larger than 1,950 bp. Transcription analysis revealed a single 2,200 nucleotide long transcript which does not contain the intron sequence.
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PMID:Partial characterization of the gene coding for subunit IV of soybean mitochondrial NADH dehydrogenase. 274 33

Mitochondrial NADH-ubiquinone oxidoreductase (complex I) is the largest enzyme of the oxidative phosphorylation system, with subunits located at the matrix and membrane domains. In plants, holocomplex I is composed of more than 40 subunits, 9 of which are encoded by the mitochondrial genome (NAD subunits). In Nicotiana sylvestris, a minor 800-kDa subcomplex containing subunits of both domains and displaying NADH dehydrogenase activity is detectable. The NMS1 mutant lacking the membrane arm NAD4 subunit and the CMSII mutant lacking the peripheral NAD7 subunit are both devoid of the holoenzyme. In contrast to CMSII, the 800-kDa subcomplex is present in NMS1 mitochondria, indicating that it could represent an assembly intermediate lacking the distal part of the membrane arm. L-galactono-1,4-lactone dehydrogenase (GLDH), the last enzyme in the plant ascorbate biosynthesis pathway, is associated with the 800-kDa subcomplex but not with the holocomplex. To investigate possible relationships between GLDH and complex I assembly, we characterized an Arabidopsis thaliana gldh insertion mutant. Homozygous gldh mutant plants were not viable in the absence of ascorbate supplementation. Analysis of crude membrane extracts by blue native and two-dimensional SDS-PAGE showed that complex I accumulation was strongly prevented in leaves and roots of Atgldh plants, whereas other respiratory complexes were found in normal amounts. Our results demonstrate the role of plant GLDH in both ascorbate biosynthesis and complex I accumulation.
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PMID:L-galactono-1,4-lactone dehydrogenase is required for the accumulation of plant respiratory complex I. 1879 60

Leber's hereditary optic neuropathy (LHON) is the maternally inherited mitochondrial disease caused by homoplasmic mutations in mitochondrial electron transport chain Complex I subunit genes. The mechanism of its incomplete penetrance is still largely unclear. In this study, we created the patient-specific human induced pluripotent stem cells (hiPSCs) from MT-ND4 mutated LHON-affected patient, asymptomatic mutation carrier and healthy control, and differentiated them into retinal ganglion cells (RGCs). We found the defective neurite outgrowth in affected RGCs, but not in the carrier RGCs which had significant expression of SNCG gene. We observed enhanced mitochondrial biogenesis in affected and carrier derived RGCs. Surprisingly, we observed increased NADH dehydrogenase enzymatic activity of Complex I in hiPSC-derived RGCs of asymptomatic carrier, but not of the affected patient. LHON mutation substantially decreased basal respiration in both affected and unaffected carrier hiPSCs, and had the same effect on spare respiratory capacity, which ensures normal function of mitochondria in conditions of increased energy demand or environmental stress. The expression of antioxidant enzyme catalase was decreased in affected and carrier patient hiPSC-derived RGCs as compared to the healthy control, which might indicate to higher oxidative stress-enriched environment in the LHON-specific RGCs. Microarray profiling demonstrated enhanced expression of cell cycle machinery and downregulation of neuronal specific genes.
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PMID:Bioactivity and gene expression profiles of hiPSC-generated retinal ganglion cells in MT-ND4 mutated Leber's hereditary optic neuropathy. 2936 7

Mitochondria, the main energy transducers in plant cells, require the proper assembly of respiratory chain complexes I-V for their function. The NADH dehydrogenase 4 (nad4) gene encodes mitochondrial respiratory chain complex I subunit IV, but the mechanism underlying nad4 transcript splicing is unclear. Here, we report that the P-type pentatricopeptide repeat (PPR) protein DEFECTIVE KERNEL 43 (DEK43) is responsible for cis-splicing of the nad4 transcript in maize. We demonstrate that DEK43 localizes to both the nucleus and mitochondria. The mutation of Dek43 resulted in embryo-lethal and light-colored defective kernels. Among the 22 mitochondrial group II introns, the splicing efficiency of nad4 introns 1 and 3 was reduced by up to 50% compared to the wild type. The levels of complex I and supercomplex I+III2 were also reduced in dek43. Furthermore, in-gel NADH dehydrogenase assays indicated that the activities of these complexes were significantly reduced in dek43. Further, the mitochondrial ultrastructure was altered in the mutant. Together, our findings indicate that DEK43, a dual-localized PPR protein, plays an important role in maintaining mitochondrial function and maize kernel development.
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PMID:DEK43 is a P-type pentatricopeptide repeat (PPR) protein responsible for the Cis-splicing of nad4 in maize mitochondria. 3111 2