Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The isolation and characterisation of a mutant affecting the assembly of mitochondrial ATPase is reported. The mutation confers resistance to oligomycin and venturicidin and sensitivity of growth on nonfermentable substrates to low temperature (19degrees). Genetic analysis indicates that the phenotype is due to a single mutation located on the mitochondrial DNA which is probably allelic with the independently isolated oligomycin resistance mutation [oli1-r]. Growth of the mutant at the non-restrictive temperature (28degrees) yields mitochondria in which the ATPase appears more sensitive to oligomycin than that of the sensitive parental strain. However, when the enzyme is isolated free from the influence of the membrane strong resistance to oligomycin is evident. These data suggest that the component responsible for the oligomycin resistance of the ATPase is part of or subject to interaction with the mitochondrial inner membrane. Measurements of the ATPase content of mitochondria indicate that ATPase production is impaired during growth at 19degreesC. In addition, studies of the maximum inhibition of mitochondrial ATPase activity by high concentrations of oligomycin suggest a selective lesion in ATPase assembly at low temperature. The nett result is that during growth at 19degrees only about 10% of the normal level of ATPase is produced of which less than half is membrane integrated and thus capable of oxidative energy production. We propose that the mutation affects a mitochondrially synthesised membrane sector peptide of the ATPase which defines the interaction of F1ATPase with specific environments on the mitochondrial inner membrane.
Mol Gen Genet 1975 Nov 03
PMID:Biogenesis of mitochondria 36, The genetic and biochemical analysis of a mitochondrially determined cold sensitive oligomycin resistant mutant of Saccharomyces cerevisiae with affected mitochondrial ATPase assembly. 12 72

The nuclear pleiotropic respiratory-deficient mutant pet1 (previously M126) exhibits cytochromes aa3 and b deficiencies accompanied by loss of the oligomycin-sensitivity of the mitochondrial ATPase. The mutant pet1, unable to grow on glycerol, growth on glucose. The latter phenotypic trait symbolized by ANAS-D, exhibits a high frequency (2 to 4 X 10(5)) Of spontaneous suppression into Antimycin A-resistant strains. Mutagenesis with MnCl2 increases by a factor of 10(2) the frequency of ANAR-D derivatives. This suppression is partial since none of the suppressed strains is able to grow on glycerol even when respiratory functions and cytochromes activities are restored as in the pet1 [SUP2] strain. In the latter strain it is concluded that the extralocus suppressor gene [SUP2] is responsible for the ANAR-D trait. Tetrad analysis in a cross homozygous for pet1 demonstrates a non-Mendelian segregation pattern for the SUP2 suppressor gene. In stable diploids, homozygous for pet1, the [SUP2] suppressor exhibits a mitotic segregation pattern. Furthermore the transmission of the [SUP2] gene is decreased by ethidium bromide treatment. Therefore, the [SUP2] suppressor gene responsible for partial suppression of the nuclear pleiotropic phenotype in mutant pet1 is of cytoplasmic heredity.
Mol Gen Genet 1976 Nov 24
PMID:A cytoplasmic gene for partial suppression of a nuclear pleiotropic respiratory deficient mutant in the petite negative yeast Schizosaccharomyces pombe. 13 78

1. Incorporation of [H3]leucine into the TCA insoluble fraction of rat liver mitochondria incubated in vitro is inhibited by uncouplers of oxidative phosphorylation. The inhibition is not correlated with the activation of mitochondrial ATPase. 2. Dependence of mitochondrial protein synthesis on the transmembrane potential is manifested in a wide range of K+ and Mg++ concentrations in the incubation media. 3. The inhibitory action of uncouplers shows a lag period equal to 5-7 minutes, this lag period however is not observed when the uncoupler is added to puromycin-treated mitochondria. 4. Dependence of mitochondrial protein synthesis on the transmembrane potential, which represents a property characteristic for the inner mitochondrial membrane suggests that mitochondrial ribosomes act in close contact with the mitochondrial membrane system.
Mol Cell Biochem 1977 Feb 04
PMID:A study of dependence of protein synthesis in mitochondria on the transmembrane potential. 14 Mar 2

1. The distribution of ATPase and several marker enzymes was examined after differential and sucrose gradient centrifugation of yeast homogenates. 2. An ATPase activity not sensitive to oligomycin is found exclusively associated with a particulate fraction equilibrating at densities of 1.23-1.25. This particulate material shows the chemical and enzymatic characteristics of the yeast plasma membrane. 3. The pH optimum of the plasma membrane ATPase is 5.6, as compared with 8.5 for the mitochondrial ATPase. In addition to oligomycin, the enzyme is not sensitive to other inhibitors of the mitochondrial ATPase as azide, dicyclohexylcarbodiimide and the mitochondrial ATPase inhibitor protein. It is inhibited by p-chloromercuryphenyl sulfonate, fluoride, quercetin and by the antibiotic Dio-9 but is not affected by ouabain. 4. The plasma membrane ATPase shows a high affinity for ATP (Km = 0.1 mM) and is very specific for this compound, hydrolyzing other nucleotide triphosphates less than 25% as rapidly. No activity was detected with ADP. 5. The enzyme requires a divalent cation for activity and Mg2+ is the most effective. It is not significantly stimulated by K+ or bicarbonate and Ca2+ is inhibitory. 6. The activity cannot be assayed in intact cells unless they are permeabilized with toluene. This suggest that the active site is on the cytoplasmic side of the plasma membrane.
Mol Cell Biochem 1978 Nov 30
PMID:Characterization of the plasma membrane ATPase of Saccharomyces cerevisiae. 15 59

The phospholipid requirement of membrane-bound enzymes may depend on several reasons. In our laboratory we have investigated lipids (1) as a bidimensional medium required for the movement of Coenzyme Q, a lipid-soluble cofactor of the mitochondrial respiratory chain, and (2) as a hydrophobic environment necessary to impose the proper conformation to membrane-bound enzymic proteins. We have found that Coenzyme Q, once reduced by NADH dehydrogenase, must cross the inner mitochondrial membrane; only quinones having long isoprenoid side chains can easily cross phospholipid bilayers, and this is the reason why a short chain quinone such as CoQ-3 inhibits NADH oxidation. The incapability of short quinones to cross lipid bilayers is due to their disposition in the lipid bilayer, stacked within the phospholipids. The conformational role of lipids has been investigated indirectly observing the kinetics of membrane-bound enzymes, e.g. the mitochondrial ATPase, and directly by circular dichroism. Lipid removal or lipid perturbation with organic solvents induce a decrease of alpha-helical content in mitochondrial proteins, and give rise to a series of kinetic changes in ATPase, including uncompetitive inhibition, increased activation energy, and loss of cooperativity in oligomycin inhibition. The recognition of a conformational role of lipids has allowed us to postulate a working hypothesis for the mechanism of action of general anesthetics. Such drugs have been found by us, by means of spin labels and fluorescent probes, to disrupt lipid protein interactions in several membranes, including synaptic membranes. The loosening of such interactions is believed to induce conformational changes, which will alter ion transport systems necessary to the propagation of neural impulses. Conformational changes induced by anesthetics have been found by us both directly by circular dichroism and indirectly by enzyme kinetics. The conformational effect of anesthetics is not directly exerted on the proteins but is mediated through the lipids. In agreement with this hypothesis we have found that membrane-bound acetylcholinesterase is inhibited by anesthetics, whereas the solubilized enzyme is not inhibited. However, binding of the solubilized enzyme to phospholipids restores anesthetic inhibition.
Mol Cell Biochem 1978 Nov 30
PMID:Biophysical studies on agents affecting the state of membrane lipids: biochemical and pharmacological implications. 15 58

This paper reviews mechanisms by which the rate of synthesis of subunits of mitochondrial inner membrane protein complexes and the assembly of these subunits are co-ordinated. Current models are evaluated and critically discussed in the light of some recent evidences. The focus is on the incorporation of cytoplasmically-synthesized cytochrome c oxidase subunits in the development of a newer model, which introduces some twists into a combination of several current ideas. A mechanism which governs both organized assembly and the co-ordination of rates of polypeptide synthesis is illustrated and the principles of the model are applied to the elucidation of some odd features of certain mutants. The possibilities that mitochondrial ATPase and cytochrome c reductase may also be synthesized and assembled according to this model are discussed.
Mol Cell Biochem 1978 May 31
PMID:Biosynthesis of mitochondrial membrane proteins: co-ordination with special reference to cytochrome c oxidase. 20 73

The mutant uvsrho 72 of Saccharomyces cerevisiae UV-sensitive for rho- production displays slower growth on media containing non-fermentable carbon sources such as glycerol or lactate. The slower growth on glycerol is not due to any deficiency in glycerol catabolism or mitochondrial oxidative phosphorylation. No modifications of the sensitivity to ethidium bromide of the mitochondrial ATPase activity could be detected. A mathematical model is presented which accounts for slower growth of uvsrho 72 on the sole basis of the continuous and elevated rho- production in the mutant strain. This model, which estimates the rate of mutation from the rate of growth and vice versa, has been verified experimentally in the case of of usvrho 72. The model has been generalised, so that it can be used for any microbial population subject to constant and high rates of any type of mutation providing that the mutant is stable, and either unable to grow or able to grow at this own rate different from that of the parental strain.
Mol Gen Genet 1978 Aug 17
PMID:Basis for slow growth on the non-fermentable substrates by a Saccharomyces cerevisiae mutant UV-sensitive for rho- production. 36 46

A mutant has been isolated which carries a nuclear mutation capable of suppressing certain aspects of the phenotype imposed by a specific mitochondrial mutation. The mitochondrial mutation [tso-r] confers cold sensitivity to growth on nonfermentable substrates and resistance to oligomycin. When both the mitochondrial and nuclear mutations are present in the same cell the cell is phenotypically cold resistant but retains a high level of oligomycin resistance. The extent of cold sensitivity suppression is dependent upon other unspecified nuclear genes. The molecular basis for the suppression may involve interactions between cytoplasmic and mitochondrial ATPase.
Mol Gen Genet 1975 Oct 22
PMID:Biogenesis of mitochondria 40. Phenotypic suppression of a mitochondrial mutation by a nuclear gene in Saccharomyces cerevisiae. 110 3

A comparative study of eight independently isolated mitochondrial oligomycin resistant mutants obtained from three laboratories show a variety of phenotypes based on cross resistance to venturicidin and sensitivity to low temperature. Analysis of recombination between pairs of markers indicate the existence of at least three genetic classes; class A, cross resistant to venturicidin and including the mutations OIII, [olil-r], [olgi-R], [tso-r]; class B, mutations OI, [olil7-r], [OLG2-R]; and class C, the mutation O11. The recombination data is consistent with mutations of each class residing in three separate genes, although mutations of class A and B show very close linkage. Recombination in non-polar crosses had demonstrated that markers of all three classes are linked to the mikl locus in the configuration (AB)-mikl-C. The mapping of this segment with respect to other markers of the mitochondrial genome and the order of classes A and B was established by analysis of co-retention frequenceis of markers in primary petite isolates as well as by analysis of marker overlap of genetically and physically defined petite genomes. The unambiguous order eryl-A-B-mik1-C-par was obtained. DNA-DNA hybridization studies using mtDNA isolated from selected petites confirms this map and estimates the physical separation of markers. A resonable correlation exists in this region of th genome between distances estimated physically by hybridization and genetically by frequencey of recombination in non-polar crosses. It is potulated that the oligomycin-mikamycin linkage group represents a cluster of genes involved in determing a number of mitochondrial membrane proteins associated with the mitochondrial ATPase and respiratory complex III.
Mol Gen Genet 1976 Apr 23
PMID:Biogenesis of mitochondria 44. comparative studies and mapping of mitochondrial oligomycin resistance mutations in yeast based on gene recombination and petite deletion analysis. 127 51

Mitochondria contain a nuclear-encoded heat shock protein, HSP60, which functions as a chaperonin in the post-translational assembly of multimeric proteins encoded by both nuclear and mitochondrial genes. We have isolated and sequenced full-length complementary DNAs coding for this mitochondrial chaperonin in Arabidopsis thaliana and Zea mays. Southern-blot analysis indicates the presence of a single hsp60 gene in the genome of A. thaliana. There is a high degree of homology at the predicted amino acid levels (43 to 60%) between plant HSP60s and their homologues in prokaryotes and other eukaryotes which indicates that these proteins must have similar evolutionarily conserved functions in all organisms. Northern- and western-blot analyses indicate that the expression of the hsp60 gene is developmentally regulated during seed germination. It is also heat-inducible. Developmental regulation of the (beta-subunit of F1-ATPase, an enzyme complex that is involved in the cyanide-sensitive mitochondrial electron transport system, indicates that imbibed embryos undergo rapid mitochondrial biogenesis through the early stages of germination. Based on the functional role of HSP60 in macromolecular assembly, these data collectively suggest that the presence of higher levels of HSP60 is necessary during active mitochondrial biogenesis, when the need for this protein is greatest in assisting the rapid assembly of the oligomeric protein structures.
Plant Mol Biol 1992 Mar
PMID:cDNA clones encoding Arabidopsis thaliana and Zea mays mitochondrial chaperonin HSP60 and gene expression during seed germination and heat shock. 134 37


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