Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human gene for the 10-kDa flavoprotein subunit of the mitochondrial NADH:ubiquinone oxidoreductase (Complex I) was completely cloned and sequenced. The so-called NDUFV3 gene contains three exons, spanning 20 kb. The open reading frame contains a 34-codon import sequence and a 74-codon mature protein sequence. A database search revealed close homology to bovine and rat protein sequence but not to any other known protein. Northern blot analysis showed that the NDUFV3 gene is ubiquitously expressed. The NDUFV3 gene was assigned by FISH to a single location on chromosome 21q22.3 and might contribute to the Down syndrome phenotype.
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PMID:Molecular cloning and characterization of the human mitochondrial NADH:oxidoreductase 10-kDa gene (NDUFV3). 934 73

Mitochondria are implicated in a variety of degenerative disorders and aging. Mitochondria are responsive to the oxygen in their environment, yet tissue culture is performed at atmospheric (21%) oxygen and not at physiological (1-11%) oxygen levels found in tissues. We employed imaging of mitochondrial probes, mass spectrometry, Western blots, and ATP assays of the human neuroblastoma cell-line SH-SY5Y and imaging of mitochondrial probes in human primary neurons under standard nonphysiological oxygen conditions (atmospheric) and under physiological oxygen levels in the nervous system to assess the impact of oxygen on mitochondrial function. SH-SY5Y cells cultured in physiological 5% oxygen exhibited the lowest reactive oxygen species (ROS) production, indicating that culture at 5% oxygen is favored; these results were mimicked in primary human cells. Mass spectrometric analysis revealed extensive mitochondrial proteomic alterations in SH-SY5Y cells based on oxygen culture condition. Among these, the rotenone-sensitive subunit of complex I NDUFV3 was increased in cells cultured at 5% oxygen. Rotenone is a Parkinson's disease-linked toxin, and correspondingly SH-SY5Y cells cultured at 5% oxygen also exhibited over 10 times greater sensitivity to rotenone than those cultured in atmospheric, 21%, oxygen. Our results indicate that neuronal mitochondria are responsive to oxygen levels and produce differential responses under different oxygen levels.
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PMID:Quantitative proteomics reveals oxygen-dependent changes in neuronal mitochondria affecting function and sensitivity to rotenone. 2397 8

Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the electron transport chain in mammalian mitochondria. Extensive proteomic and structural analyses of complex I from Bos taurus heart mitochondria have shown it comprises 45 subunits encoded on both the nuclear and mitochondrial genomes; 44 of them are different and one is present in two copies. The bovine heart enzyme has provided a model for studying the composition of complex I in other mammalian species, including humans, but the possibility of additional subunits or isoforms in other species or tissues has not been explored. Here, we describe characterization of the complexes I purified from five rat tissues and from a rat hepatoma cell line. We identify a~50kDa isoform of subunit NDUFV3, for which the canonical isoform is only ~10kDa in size. We combine LC-MS and MALDI-TOF mass spectrometry data from two different purification methods (chromatography and immuno-purification) with information from blue native PAGE analyses to show the long isoform is present in the mature complex, but at substoichiometric levels. It is also present in complex I in cultured human cells. We describe evidence that the long isoform is more abundant in both the mitochondria and purified complexes from brain (relative to in heart, liver, kidney and skeletal muscle) and more abundant still in complex I in cultured cells. We propose that the long 50kDa isoform competes with its canonical 10kDa counterpart for a common binding site on the flavoprotein domain of complex I.
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PMID:Subunit NDUFV3 is present in two distinct isoforms in mammalian complex I. 2794 20

Human mitochondrial complex I is the first enzyme of the mitochondrial respiratory chain. Complex I is composed of 45 subunits, seven encoded by mitochondrial DNA, while the remainder are encoded by nuclear DNA. All nuclear-encoded subunits are thought to be expressed as a single isoform. Here we reveal subunit NDUFV3 to be present in both the canonical 10 kDa and a novel 50 kDa isoform, generated through alternative splicing. Both isoforms assemble into complex I and their levels vary in different tissues. While the 50 kDa isoform appears to be dominant in HEK293T cells, we find either isoform alone is sufficient for assembly of mature complex I. NDUFV3 represents the first known complex I subunit present in two functional isoforms.
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PMID:A novel isoform of the human mitochondrial complex I subunit NDUFV3. 2798 11

Mitochondrial complex I is the largest respiratory chain complex. Despite the enormous progress made studying its structure and function in recent years, potential regulatory roles of its accessory subunits remained largely unresolved. Complex I gene NDUFV3, which occurs in metazoa, contains an extra exon that is only present in vertebrates and thereby evolutionary even younger than the rest of the gene. Alternative splicing of this extra exon gives rise to a short NDUFV3-S and a long NDUFV3-L protein isoform. Complexome profiling revealed that the two NDUFV3 isoforms are constituents of the multi-subunit complex I. Further mass spectrometric analyses of complex I from different murine and bovine tissues showed a tissue-specific expression pattern of NDUFV3-S and NDUFV3-L. Hence, NDUFV3-S was identified as the only isoform in heart and skeletal muscle, whereas in liver, brain, and lung NDUFV3-L was expressed as the dominant isoform, together with NDUFV3-S present in all tissues analyzed. Thus, we identified NDUFV3 as the first out of 30 accessory subunits of complex I present in vertebrate- and tissue-specific isoforms. Interestingly, the tissue-specific expression pattern of NDUFV3-S and NDUFV3-L isoforms was paralleled by changes in kinetic parameters, especially the substrate affinity of complex I. This may indicate a regulatory role of the NDUFV3 isoforms in different vertebrate tissues.
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PMID:Identification and evolutionary analysis of tissue-specific isoforms of mitochondrial complex I subunit NDUFV3. 2798 83