Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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A nuclear gene mutant of Neurospora crassa designated cyb-3 is deficient in cytochrome b and coenzyme QH2-cytochrome c reductase. Nearly normal when grown at 25 degrees C, the strain expresses a mutant phenotype at 38 degrees C. Mitochondria from cyb-3 mycelium, which has undergone 3-4 mass doublings at the elevated temperature, possess 3-fold less cytochrome b, 2-fold more cytochrome, c, 5-fold less coenzyme QH2-cytochrome c reductase activity, and require 3-fold less antimycin A per milligram of protein to inhibit NADH oxidation that do wild type mitochondria. The activity of coenzyme QH2-cytochrome c reductase declines rather slowly in cultures of cyb-3 transferred to 38 degrees C, and the in vitro thermostability of the enzyme is very similar in wild type and mutant mitochondria. Therefore, the mutation may decrease synthesis of impair integration into the membrane of cytochrome b and perhaps other proteins of the enzyme comple.
Mol Gen Genet 1977 Mar 28
PMID:A temperature-sensitive mutant of Neurospora crassa deficient in cytochrome b. 14 Oct 3

Nineteen mutants of S. cerevisiae exhibiting a double deficiency in cytochrome oxidase and coenzyme QH2-cytochrome c reductase (also cytochrome b deficient) have been studied. The mutants have been crossed to a set of rho- tester strains with different segments of mitochondrial DNA. The mutants have also been crossed to mit- testers with defined genetic lesions. In addition, crosses were performed with a respiratory competent strain to ascertain whether mitotic and meiotic segregants could be isolated with only one of the two enzymatic deficiencies. The rho- testers allowed the doubly deficient mutants to be separated into two classes. Mutants in class 1 were not restored by any of the rho- testers and appeared to have separate mutations, one in cytochrome oxidase and the other in cytochrome b. Mutants in class 2 were restored by a set of rho- clones whose retained segments of mitochondrial DNA contained the cytochrome b but not the cytochrome oxidase loci. These appeared to behave as single hit mutations. Further studies, however, indicated that both class 1 and class 2 mutants carried separate mutations in two different loci. Mitotic and meiotic segregants with a single enzymatic deficiency could be isolated. In a number of strains, the mutations were mapped in known cytochrome oxidase and cytochrome b loci. The apparent discrepancy of the rho- tests for the class 2 mutants was shown to be probably due to a high unstability in one of the mutations. It has been concluded that all the doubly deficient strains carry two mutations in previously described cytochrome oxidase and cytochrome b loci. This conclusion argues against the existence of a single gene on mitochondrial DNA that controls the biosynthesis of the two respiratory enzymes.
Mol Gen Genet 1976 Nov 24
PMID:Assembly of the mitochondrial membrane system. XIX. Genetic characterization of mit- mutants with deficiencies in cytochrome oxidase and coenzyme qh2-cytochrome c reductase. 18 77

Diuron-resistance, DIU (Colson et al., 1977), antimycin-resistance, ANA (Michaelis, 1976; Burger et al., 1976), funiculosin-resistance, FUN (Pratje and Michaelis, 1977; Burger et al., 1977) and mucidin-resistance, MUC (Subik et al., 1977) are each coded by a pair of genetic loci on the mit DNA of S. cerevisiae. In the present paper, these respiratiory-competent, drug-resistant loci are localized relative to respiratory-deficient BOX mutants deficient in coenzyme QH2-cytochrome c reductase (Kotylak and Slonimski, 1976, 1977) using deletion and recombination mapping. Three drug-resistant loci possessing distinct mutated allelic forms are distinguished. DIU1 is allelic or closely linked to ANA2, FUN1 and BOX1; DIU2 is allelic or closely linked to ANA1, MUC1 and BOX4/5; MUC2 is allelic to BOX6. The high recombinant frequencies observed between the three loci (13% on the average for 33 various combinations analyzed) suggest the existence of either three genes coding for three distinct polypeptides or of a single gene coding for a single polypeptide but subdivided into three easily separable segments. The resistance of the respiratory-chain observed in vitro in the drug-resistant mutants and the allelism relationships between respiratory-competent, drug-resistant loci and coQH2-cyt c reductase deficient, BOX, loci strongly suggest that each of the three drug-resistant loci codes for a structural gene-product which is essential for the normal coQH2-cyt c reductase activity and is obviously a good candidate for a gene product of the drug-resistant loci mapped in this paper. Polypeptide length modifications of cytochrome b were observed in mutants deficient in the coQH2-cyt c red and localized at the BOX1, BOX4 and BOX6 genetic loci (Claisse et al., 1977, 1978) which are precisely the loci allelic to drug resistant mutants as shown in the present work. Taken together these two sets of data provide a strong evidence in favor of the idea that there exist three non contiguous segments of the mitochondrial DNA sequence which code for a single polypeptide sequence of cytochrome b. In each segment mutations which modify the polypeptide sequence can occur leading to the loss (BOX mutants) or to a modification (drug resistant mutants) of the enzyme activity.
Mol Gen Genet 1979 Jan 02
PMID:Genetic localization of diuron- and mucidin-resistant mutants relative to a group of loci of the mitochondrial DNA controlling coenzyme QH2-cytochrome c reductase in Saccharomyces cerevisiae. 36 93

The role of mitochondrial protein synthesis, electron transport, and four specific mitochondrial gene products on sporulation were studied in respiratory deficient mit- mutants. These mutants were isolated in an op 1 strain and localized on the mitochondrial genome by petite deletion mapping. All 153 mutations studied could be assigned to the four mitochondrial regions OXI1, OXI2, OXI3 and COB, known to affect cytochrome c oxidase and cytochrome b. The specific loss of one mitochondrially translated polypeptide was found in some mutants of each locus: OXI1--cytochrome c oxidase subunit 2, OXI2--subunit 3, OXI3--subunit 1, and COB--cytochrome b. The ability of diploid mit- mutants to sporulate was systematically investigated. About one third of the mutants, representing three loci, were incapable of forming spores. All other cultures produced either respiratory competent mit+ tetrads, both mit+ and mit- tetrads, or only mit- tetrads. Mutants forming mit- tetrads mapped in all four loci. These results demonstrate that in contrast to petite mutants some mit- mutants have retained the ability to perform meiosis and sporulation.
Mol Gen Genet 1979 Nov
PMID:Sporulation of mitochondrial respiratory deficient mit- mutants of Saccharomyces cerevisiae. 39 41

Commercial preparations of mikamycin have been shown to act as both inhibitors of mitochondrial protein synthesis and respiration. These preparations are shown to consist of two major streptogramin components (mikamycin A and mikamycin B) and a number of minor components. The major streptogramin components which inhibit mitochondrial protein synthesis in vitro are without effect in vivo due to whole cell impermeability to these compounds. A minor antimycin A-like component is the active compound in mikamycin preparations which inhibits growth of yeast cells on ethanol. The site of this inhibition is at the level of respiratory Comples III. The mitochondrial [mik 1-r] mutation confers resistance to this minor growth inhibitory component and cross resistance to antimycin A. For clarity the designation mik 1 has therefore been renamed ana 1 to denote the mitochondrial determinant conferring resistance to antimycin A. Genetic and physical mapping studies localise the ana 1 determinant in the region of mitochondrial DNA specifying cytochrome b. It is proposed that the ana 1 locus is part of a gene specifying a membrane component of Complex III.
Mol Gen Genet 1977 Mar 07
PMID:Biogenesis of mitochondria 48: mikamycin resistance in Saccharomyces cerevisiae--a mitochondrial mutation conferring resistance to an antimycin A-like contaminant in mikamycin. 40 12

1. Fourteen cytoplasmic mutants of Saccharomyces cerevisiae with a specific deficiency of cytochrome b have been studied. The mutations have been shown to occur in two separate genetic loci, COB 1 and COB 2. These loci can be distinguished by mit- X mit- crosses. Pairwise crosses of cytochrome b mutants belonging to different loci yield 4-6% wild type recombinants corresponding to recombinational frequencies of 8-12%. In intra-locus crosses, the recombinational frequencies range from 1% to less than 0.01%. The two loci can also be distinguished by mit- X rho- crosses. Twenty rho- testers have been isolated of which ten preferentially restore mutations in COB 1 and ten others in COB 2. 2. The COB 1 and COB 2 loci have been localized on mitochondrial DNA between the two antibiotic resistance loci OLI 1 and OLI 2 in the order OLI 2-COB 2-COB 1-OLI 1. The results of mit- X mit- and mit- X rho- crosses have also been used to map the cytochrome b mutations relative to each other. The maps obtained by the two independent methods are in good agreement. 3. Mutations in COB 1 have been found to be linked to the OLI1 locus in some but not in other strains of S. cervisiae. This evidence suggests that there may be a spacer region between the two loci whose length varies from strain to strain. 4. Two mutations in COB 2 have been found to cause a loss of a mitochondrial translation product corresponding to the cytochrome b apoprotein. Instead of the wild type protein the mutants have a new low-molecular weight product which is probably a fragment of cytochrome b. The fact that the mutations revert suggests that they are nonsense mutations in the structural gene of cytochrome b.
Mol Gen Genet 1976 Nov 24
PMID:Assembly of the mitochondrial membrane system. XVIII. Genetic loci on mitochondrial DNA involved in cytochrome b biosynthesis. 79 70

We were able to differentiate between species of billfish (Istiophoridae family) and to detect considerable intraspecific variation in the blue marlin (Makaira nigricans) by directly sequencing a polymerase chain reaction (PCR)-amplified, 612-bp fragment of the mitochondrial cytochrome b gene. Thirteen variable nucleotide sites separated blue marlin (n = 26) into 7 genotypes. On average, these genotypes differed by 5.7 base substitutions. A smaller sample of swordfish from an equally broad geographic distribution displayed relatively little intraspecific variation, with an average of 1.3 substitutions separating different genotypes. A cladistic analysis of blue marlin cytochrome b variants indicates two major divergent evolutionary lines within the species. The frequencies of these two major evolutionary lines differ significantly between Atlantic and Pacific ocean basins. This finding is important given that the Atlantic stocks of blue marlin are considered endangered. Migration from the Pacific can help replenish the numbers of blue marlin in the Atlantic, but the loss of certain mitochondrial DNA haplotypes in the Atlantic due to overfishing probably could not be remedied by an influx of Pacific fish because of their absence in the Pacific population. Fishery management strategies should attempt to preserve the genetic diversity within the species. The detection of DNA sequence polymorphism indicates the utility of PCR technology in pelagic fishery genetics.
Mol Mar Biol Biotechnol 1992 Jun
PMID:Direct sequencing of mitochondrial DNA detects highly divergent haplotypes in blue marlin (Makaira nigricans). 130 4

The intron-encoded proteins bI4 RNA maturase and aI4 DNA endonuclease can be faithfully expressed in yeast cytoplasm from engineered forms of their mitochondrial coding sequences. In this work we studied the relationships between these two activities associated with two homologous intron-encoded proteins: the bI4 RNA maturase encoded in the fourth intron of the cytochrome b gene and the aI4 DNA endonuclease (I-SceII) encoded in the fourth intron of the gene coding for the subunit I of cytochrome oxidase. Taking advantage of both the high recombinogenic properties of yeast and the similarities between the two genes, we constructed in vivo a family of hybrid genes carrying parts of both RNA maturase and DNA endonuclease coding sequences. The presence of a sequence coding for a mitochondrial targeting peptide upstream from these hybrid genes allowed us to study the properties of their translation products within the mitochondria in vivo. We thus could analyze the ability of the recombinant proteins to complement RNA maturase deficiencies in different strains. Many combinations of the two parental intronic sequences were found in the recombinants. Their structural and functional analysis revealed the following features. (i) The N-terminal half of the bI4 RNA maturase could be replaced in total by its equivalent from the aI4 DNA endonuclease without affecting the RNA maturase activity. In contrast, replacing the C-terminal half of the bI4 RNA maturase with its equivalent from the aI4 DNA endonuclease led to a very weak RNA maturase activity, indicating that this region is more differentiated and linked to the maturase activity. (ii) None of the hybrid proteins carrying an RNA maturase activity kept the DNA endonuclease activity, suggesting that the latter requires the integrity of the aI4 protein. These observations are interesting because the aI4 DNA endonuclease is known to promote the propagation, at the DNA level, of the aI4 intron, whereas the bI4 RNA maturase, which is required for the splicing of its coding intron, also controls the splicing process of the aI4 intron. We propose a scenario for the evolution of these intronic proteins that relies on a switch from DNA endonuclease to RNA maturase activity.
Mol Cell Biol 1992 Feb
PMID:Connections between RNA splicing and DNA intron mobility in yeast mitochondria: RNA maturase and DNA endonuclease switching experiments. 131 Jan 49

We have compared kinetoplast DNA maxicircles of tunicamycin- and arsenite-resistant variants of repeatedly cloned Leishmania mexicana amazonensis showing DNA amplification with wild-type and arsenite-resistant variants of the same lineage that do not show DNA amplification. DNA restriction patterns and the degree of cross-hybridization between maxicircle DNA fragments of parasites displaying DNA amplification and those of parasites without amplification were examined. In addition, the nucleotide sequence of the cytochrome b (Cyb) gene from the coding region was compared between these two groups of parasites. Extensive changes were found in the nucleotide sequences and the amino acid sequences of the cytochrome gene of the maxicircles of variants with DNA amplification. The Cyb genes from both groups had much shorter open reading frames than the same gene from Leishmania tarentolae and Trypanosoma brucei. The simultaneous changes in maxicircles and minicircles of these variants suggest that they may confer the advantage of maintaining viable mitochondrial function under selective pressure.
Mol Biochem Parasitol 1992 Dec
PMID:Characterization of sequence changes in kinetoplast DNA maxicircles of drug-resistant Leishmania. 133 69

Relationships among members representing each of the three subgenera of the Middle American rodent genus Orthogeomys (Rodentia: Geomyidae) were studied by comparing DNA sequence data from two regions of the mitochondrial genome. Results from 527 bp from the 16 S rDNA region and a 402-bp fragment of the cytochrome b gene indicate that the three subgenera are well differentiated genetically, with the subgenus Orthogeomys being distantly related to Macrogeomys and Heterogeomys, and Macrogeomys appearing as the most derived. Within the subgenus Macrogeomys, O. heterodus and O. cherriei form a distinct clade, as do O. dariensis and O. cavator. As with previous protein-electrophoretic studies, the placement of O. underwoodi could not be determined definitively within the subgenus Macrogeomys. We interpret our inability to determine phylogenetic relationships among these three clades as evidence for a rapid phyletic radiation within this subgenus. Sequence divergence estimates indicate that the Macrogeomys radiation took place following the time of completion of the Panamanian land bridge (1.9-2.9 mya). Additionally, the near identity of sequences of a newly described species, O. thaeleri, with those of O. dariensis (percentage sequence divergence = 0.3%) suggests that the two may be conspecific.
Mol Phylogenet Evol 1992 Mar
PMID:Phylogenetic relationships among middle American pocket gophers (genus Orthogeomys) based on mitochondrial DNA sequences. 134 19


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