Identification of the subunits of bovine NADH dehydrogenase which are encoded by the mitochondrial genome

Gibb, G M; Ragan, C I

doi:10.1042/bj2650903

Cited by 15 publications

(6 citation statements)

References 19 publications

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“…An environmental toxin with uptake and conversion characteristics similar to MPTP could inhibit complex I activity directly by binding to one or more of its polypeptides. Rotenone, for instance, which also produces nigrostriatal dopaminergic cell death when injected stereotactically into rats (Heikkila et al, 1985), inhibits complex I by direct binding to a site which includes two mitochondrially encoded polypeptides M, 33,000 and 5 1,000 (Gibb and Ragan, 1990). Recent work has shown increased lipid peroxidation and increased levels of mitochondrial superoxide dismutase in Parkinson substantia nigra Saggu et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Anatomic and Disease Specificity of NADH CoQ₁ Reductase (Complex I) Deficiency in Parkinson's Disease

Schapira

Mann

Cooper

et al. 1990

Journal of Neurochemistry

634

263

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is thought to produce parkinsonism in humans and other primates through its inhibition of complex I. The recent discovery of mitochondrial complex I deficiency in the substantia nigra of patients with Parkinson's disease has provided a remarkable link between the idiopathic disease and the action of the neurotoxin MPTP. This article shows that complex I deficiency in Parkinson's disease is anatomically specific for the substantia nigra, and is not present in another neurodegenerative disorder involving the substantia nigra. Evidence is also provided to show that there is no correlation between L-3,4-dihydroxyphenylalanine therapy and complex I deficiency. These results suggest that complex I deficiency may be the underlying cause of dopaminergic cell death in Parkinson's disease.

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Section: Discussionmentioning

confidence: 99%

Anatomic and Disease Specificity of NADH CoQ₁ Reductase (Complex I) Deficiency in Parkinson's Disease

Schapira

Mann

Cooper

et al. 1990

Journal of Neurochemistry

634

263

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“…It has been purified from chloroform/methanol extracts of bovine mitochondria, and shown to have an apparent molecular mass on PAGE of about 39 kDa (Fearnley & Walker, 1987). A product with a molecular mass of 39 kDa has also been observed in bovine mitochondria radiolabelled in the presence of cycloheximide (Gibb & Ragan, 1990). Therefore it has been proposed that the 39 kDa band observed in Coomassie Bluestained gels of complex I and the hydrophobic protein fraction is a mitochondrial gene product (Ragan, 1987), whereas we have characterized a nuclear-coded subunit of complex I from the 39 kDa band.…”

Section: -mentioning

confidence: 99%

NADH:ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits

Fearnley

Finel

Skehel

et al. 1991

Biochemical Journal

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The 39 kDa and 42 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria are nuclear-coded components of the hydrophobic protein fraction of the enzyme. Their amino acid sequences have been deduced from the sequences of overlapping cDNA clones. These clones were amplified from total bovine heart cDNA by means of the polymerase chain reaction, with the use of complex mixtures of oligonucleotide primers based upon fragments of protein sequence determined at the N-terminals of the proteins and at internal sites. The protein sequences of the 39 kDa and 42 kDa subunits are 345 and 320 amino acid residues long respectively, and their calculated molecular masses are 39,115 Da and 36,693 Da. Both proteins are predominantly hydrophilic, but each contains one or two hydrophobic segments that could possibly be folded into transmembrane alpha-helices. The bovine 39 kDa protein sequence is related to that of a 40 kDa subunit from complex I from Neurospora crassa mitochondria; otherwise, it is not related significantly to any known sequence, including redox proteins and two polypeptides involved in import of proteins into mitochondria, known as the mitochondrial processing peptidase and the processing-enhancing protein. Therefore the functions of the 39 kDa and 42 kDa subunits of complex I are unknown. The mitochondrial gene product, ND4, a hydrophobic component of complex I with an apparent molecular mass of about 39 kDa, has been identified in preparations of the enzyme. This subunit stains faintly with Coomassie Blue dye, and in many gel systems it is not resolved from the nuclearcoded 36 kDa subunit.

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“…Although not all of the mitochondrial translation products are visible on this autoradiogram, the polypeptide pattern resembles that for cultured skin fibroblasts (Beattie and Sen, 1987). The bands are recognizable as ND5 (apparent molecular mass 51 kDa), COI (apparent molecular mass 44 kDa), ND4 (apparent molecular mass 39 kDa), cytochrome b (apparent molecular mass 35 kDa), NDI and ND2 (apparent molecular mass 30 and 33 kDa) and COII/III, which co-migrate at a molecular mass of 18-20 kDa (Hare et al, 1980;Gibb and Ragan, 1990).…”

Section: Mitochondrial Protein Synthesismentioning

confidence: 99%

Respiratory-deficient human fibroblasts exhibiting defective mitochondrial DNA replication

Bodnar

Cooper

Leonard³

et al. 1995

Biochemical Journal

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We have characterized cultured skin fibroblasts from two siblings affected with a fatal mitochondrial disease caused by a nuclear genetic defect. Mitochondrial respiratory-chain function was severely decreased in these cells. Southern-blot analysis showed that the fibroblasts had reduced levels of mitochondrial DNA (mtDNA). The mtDNA was unstable and was eliminated from the cultured cells over many generations, generating the rho0 genotype. As the mtDNA level decreased, the cells became more dependent upon pyruvate and uridine for growth. Nuclear-encoded subunits of respiratory-chain complexes were synthesized and imported into the mitochondria of the mtDNA-depleted cells, albeit at reduced levels compared with the controls. Mitochondrial protein synthesis directed by the residual mtDNA indicated that the mtDNA was expressed and that the defect specifically involves the replication or maintenance of mtDNA. This is a unique example of a respiratory-deficient human cell line exhibiting defective mtDNA replication.

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Identification of the subunits of bovine NADH dehydrogenase which are encoded by the mitochondrial genome

Cited by 15 publications

References 19 publications

Anatomic and Disease Specificity of NADH CoQ₁ Reductase (Complex I) Deficiency in Parkinson's Disease

Anatomic and Disease Specificity of NADH CoQ₁ Reductase (Complex I) Deficiency in Parkinson's Disease

NADH:ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits

Respiratory-deficient human fibroblasts exhibiting defective mitochondrial DNA replication

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Identification of the subunits of bovine NADH dehydrogenase which are encoded by the mitochondrial genome

Cited by 15 publications

References 19 publications

Anatomic and Disease Specificity of NADH CoQ1 Reductase (Complex I) Deficiency in Parkinson's Disease

Anatomic and Disease Specificity of NADH CoQ1 Reductase (Complex I) Deficiency in Parkinson's Disease

NADH:ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits

Respiratory-deficient human fibroblasts exhibiting defective mitochondrial DNA replication

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Product

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Anatomic and Disease Specificity of NADH CoQ₁ Reductase (Complex I) Deficiency in Parkinson's Disease

Anatomic and Disease Specificity of NADH CoQ₁ Reductase (Complex I) Deficiency in Parkinson's Disease