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At least 253 records · Page 14Linked to original sources
PubMed1997

Mitochondrial DNA sequence divergence in weevils of the Pissodes strobi species complex (Coleoptera:Curculionidae).

Mitochondrial DNA sequence divergence is unusually high between several species of the Pissodes strobi complex, in contrast to low allozyme and morphological divergences, and the ability to hybridize in the laboratory. We sequenced an 810 bp segment in seven individuals, representing four species in the P. strobi complex and one outgroup species, P. affinis Randall. The 810 bp segment covered the 3' half of the cytochrome oxidase subunit I (COI) gene. We also sequenced one specimen of P. strobi (Peck) over a 2301 bp region of mtDNA, extending from the 5' end of COI to the 3' end of COII. Uncorrected sequence divergences were below 1.1% among three specimens of P. schwarzi Hopkins, and between P. terminalis Hopping and P. nemorensis Germar. All other interspecific combinations in the P. strobi complex showed divergences of 6.0-7.5%. The outgroup species, P. affinis, had an average divergence of 12.8% from members of the P. strobi group. As in most other insects, A + T content in Pissodes mtDNA was high; transition:transversion ratio was high among lineages exhibiting low divergences, but declined with increasing sequence divergence; and inferred amino acid sequence divergences were low. The degree of sequence divergence differs markedly across different functional regions of the COI gene. The high mtDNA divergences within the P. strobi complex calculated from direct sequencing support earlier reports based on restriction site surveys; however, cladograms based on mtDNA sequence differ from those based on earlier work.

Amino Acids↗
PubMed2002

Perfluorooctanoate, perflourooctanesulfonate, and N-ethyl perfluorooctanesulfonamido ethanol; peroxisome proliferation and mitochondrial biogenesis.

Compounds that cause peroxisome proliferation in rats and mice have been reported to interfere with mitochondrial (mt) bioenergetics and possibly biogenesis. The purpose of this investigation was to establish whether proliferation of peroxisomes and mitochondria are necessarily related. Perfluorooctanesulfonate (PFOS) and N-ethyl perfluorooctanesulfonamido ethanol (N-EtFOSE) were investigated as peroxisome proliferators in comparison to perfluorooctanoic acid (PFOA). Three parameters were chosen to assess peroxisome proliferation, stimulation of lauroyl CoA oxidase activity, reduction of serum cholesterol concentration, and hepatomegaly. mt Biogenesis was assessed through cytochrome oxidase activity, cytochrome content and mitochondrial DNA (mtDNA) copy number. PFOA, PFOS, or N-EtFOSE was administered via a single i.p. injection at 100 mg/kg in male rats, and measurements were made 3 days later. In this model, PFOS and PFOA share similar potencies as peroxisome proliferators, whereas N-EtFOSE showed no activity. mt Endpoints were altered only in the PFOA treatment group, which consisted of a decrease cytochrome oxidase activity in liver tissue and an increase in the mtDNA copy number. None of the perfluorooctanoates significantly altered mt cytochrome content following acute in vivo treatment. These data demonstrate that acute administration of PFOS or PFOA causes hepatic peroxisome proliferation in rats. However, stimulation of mt biogenesis is not a characteristic response of all peroxisome proliferators.

Acyl-CoA Dehydrogenase↗
PubMed1994

Phylogeny of the Drosophila obscura species group deduced from mitochondrial DNA sequences.

Approximately 2 kb corresponding to different regions of the mtDNA of 14 different species of the obscura group of Drosophila have been sequenced. In spite of the uncertainties arising in the phylogenetic reconstruction due to a restrictive selection toward a high mtDNA A+T content, all the phylogenetic analysis carried out clearly indicate that the obscura group is formed by, at least, four well-defined lineages that would have appeared as the consequence of a rapid phyletic radiation. Two of the lineages correspond to monophyletic subgroups (i.e., affinis and pseudoobscura), whereas the obscura subgroup remains heterogeneous assemblage that could be reasonably subdivided into at least two complexes (i.e., subobscura and obscura).

Animals↗
PubMed1999

Current intraspecific dynamics of sequence evolution differs from long-term trends and can account for the AT-richness of honeybee mitochondrial DNA.

The very high AT content of hymenopteran mtDNA has warranted speculation about nucleotide substitution processes in this group. Here we investigate the pattern of honeybee, Apis mellifera, mtDNA nucleotide polymorphisms inferred from phylogeny in terms of differences between the ATPase6, COI, COII, COIII, cytochrome b, and ND2 genes and strand asymmetry in mutation rates. The observed transition/transversion ratios and the distribution of nonsynonymous substitutions between regions differed significantly. The pattern of differences between genes leading to these heterogeneities (the ATPase6 and COIII genes group apart from the rest) differed markedly from that predicted on the basis of long-term evolutionary change and may indicate differences between current and long-term dynamics of sequence evolution. Also, there is strong strand asymmetry in substitutions, which probably results in a mutability of G and C sufficiently high to account for the AT-richness of honeybee mtDNA.

Adenosine Triphosphatases↗
PubMed2004

Mitochondrial DNA organisation of the mtDNA type 2b of Aspergillus tubingensis compared to the Aspergillus niger mtDNA type 1a.

A physical and functional map of Aspergillus tubingensis mtDNA type 2b was constructed and compared to Aspergillus niger typeI a mtDNA. The gene content and order, as well as the patterns of restriction sites, were similar. Two unidentified ORFs and several repeat elements were found in the region between the ndhl and ndh4 genes on both mtDNAs. The sizes of the A. niger and A. tubingensis mtDNAs were 31.23 and 33.06 kb. respectively, the difference was principally attributed to the altered intron content of their coxl genes.

Aspergillus↗
PubMed2004

Mutations in AAC2, equivalent to human adPEO-associated ANT1 mutations, lead to defective oxidative phosphorylation in Saccharomyces cerevisiae and affect mitochondrial DNA stability.

Autosomal dominant and recessive forms of progressive external ophthalmoplegia (adPEO and arPEO) are mitochondrial disorders characterized by the presence of multiple deletions of mitochondrial DNA in affected tissues. Four adPEO-associated missense mutations have been identified in the ANT1 gene. In order to investigate their functional consequences on cellular physiology, we introduced three of them at equivalent positions in AAC2, the yeast orthologue of human ANT1. We demonstrate here that expression of the equivalent mutations in aac2-defective haploid strains of Saccharomyces cerevisiae results in (a) a marked growth defect on non-fermentable carbon sources, and (b) a concurrent reduction of the amount of mitochondrial cytochromes, cytochrome c oxidase activity and cellular respiration. The efficiency of ATP and ADP transport was variably affected by the different AAC2 mutations. However, irrespective of the absolute level of activity, the AAC2 pathogenic mutants showed a significant defect in ADP versus ATP transport compared with wild-type AAC2. In order to study whether a dominant phenotype, as in humans, could be observed, the aac2 mutant alleles were also inserted in combination with the endogenous wild-type AAC2 gene. The heteroallelic strains behaved as recessive for oxidative growth and petite-negative phenotype. In contrast, reduction in cytochrome content and increased mtDNA instability appeared to behave as dominant traits in heteroallelic strains. Our results indicate that S. cerevisiae is a suitable in vivo model to study the pathogenicity of the human ANT1 mutations and the pathophysiology leading to impairment of oxidative phosphorylation and damage of mtDNA integrity, as found in adPEO.

Adenine Nucleotide Translocator 1↗
PubMed2006

Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice.

When pyrroloquinoline quinone (PQQ) is added to an amino acid-based, but otherwise nutritionally complete basal diet, it improves growth-related variables in young mice. We examined PQQ and mitochondrial function based on observations that PQQ deficiency results in elevated plasma glucose concentrations in young mice, and PQQ addition stimulates mitochondrial complex 1 activity in vitro. PQQ-deficient weanling mice had a 20-30% reduction in the relative amount of mitochondria in liver; lower respiratory control ratios, and lower respiratory quotients than PQQ-supplemented mice (2 mg PQQ/kg diet). In mice from dams fed a conventional laboratory diet, but switched at weaning to the basal diet, plasma glucose, Ala, Gly, and Ser concentrations were elevated at 4 wk (PQQ- vs. PQQ+), but not at 8 wk. The relative mitochondrial content (ratio of mtDNA to nuclear DNA) also tended (P<0.18) to be lower (PQQ- vs. PQQ+) at 4 wk, but not at 8 wk. PQQ also counters the mitochondrial complex 1 inhibitor, diphenylene iodonium (DPI). Mice were gavaged with 0, 0.4, or 4 microg PQQ/g body weight (BW) daily for 14 d. At each PQQ level, DPI was injected (i.p.) at 0, 0.4, 0.8, or 1.6 microg DPI/g BW. The PQQ-deficient mice exposed to 0.4 or 4.0 microg DPI/g lost weight and had lower plasma glucose levels than PQQ-supplemented mice (P<0.05). In addition, fibroblasts took up (3)H-PQQ added to cell cultures, and cultured hepatocytes maintained mitochondrial PQQ concentrations similar to those observed in vivo. Collectively, these results indicate that dietary PQQ can influence mitochondrial amount and function, particularly in perinatal and weanling mice.

Amino Acids↗
PubMed1977

Structure of animal mitochondrial DNA (base composition, pyrimidine clusters, character of methylation).

Base composition, content of pyrimidine isopliths and methylation degree of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) from various vertebrates and protozoon Crithidia oncopelti have been studied. mtDNAs from mammals (ox, rat) do not differ in fact in the G + C content from the respective nDNA. The G + C content in mtDNA from fishes (sheat-fish) and birds (duck, chicken) is 1.5--2.5 mol % higher than in the respective nDNA. Kinetoplast DNA (kDNA) from Crithidia oncopelti (G + C = 42.9 mol %) differs significantly in base composition from nDNA (G + C 51.3 mol%). All the mtDNA and kDNA studied differ from the respective nDNA by a lower degree of pyrimidine clustering. The amount of mono- and dipyrimidine fragments in mtDNA is more than 30 mol %, whereas in nDNA it does not exceed 23 mol %. The quantity of long pyrimidine clusters (hexa- and others) is 2--4 times lower in mtDNA than in nDNA. The lower degree of clustering of pyrimidine nucleotides seems to be a specific feature of all the mtDNA studied. This may be indicative of common traits in the organization and origin of mtDNA. All mtDNA of vertebrates contain 5-methylcytosine as "minor" base (1.5--3.15 mol %) and surpass by 1.5--2 times the respective nDNA in the methylation degree. It has been found that in animals mtDNA is species specific as far as the 5-methylcytosine content is concerned. mtDNA of beef heart differs significantly from nDNA in the mode of 5-methylcytosine distribution in pyrimidine isopliths, which may indicate that methylation specificity of nuclear and mitochondrial DNA is not the same. In mitochondria and nuclei of rat liver certain DNA-methylase activity has been detected, which provides in vitro the methylation of cytosine residues both in homologbous DNA and various heterologous DNAs. Specificity of methylation in vitro of cytosine residues in one and the same heterologous DNA from Escherichia coli B with nuclear and mitochondrial enzymes is different. Mitochondrial enzyme methylates cytosine residues chiefly in mono-, whereas nuclear enzyme, in di- and tripyrimidine fragments.

Animals↗
PubMed1993

Molecular and genetic analyses of two patients with Pearson's marrow-pancreas syndrome.

Pearson's syndrome, a rare and fatal disorder characterized by refractory sideroblastic anemia and pancreatic insufficiency in infancy, is classified into mitochondrial cytopathies. To understand the molecular and genetic bases of this disorder, we have investigated the mitochondrial respiratory chain enzymes and the mitochondrial DNA (mtDNA) in two Japanese patients with Pearson's syndrome. Immunoblot analysis from various tissues showed the different grades of defects in the subunits of respiratory enzyme complexes. The analyses of mtDNA showed that the deletion in patient 1 spanned 4977 bp from the ATPase 8 gene to the NADH dehydrogenase 5 gene between 13-bp direct repeats, whereas the deletion in patient 2 spanned 3151 bp from the transfer RNA(His) gene to the cytochrome b gene unrelated to any repeated sequences. The deleted mtDNA was heteroplasmic in all the analyzed tissues, but the proportions of deleted mtDNA were quite different. We observed a tendency for the tissue with low percentages of normal-sized mtDNA to show low contents of complex I subunits. Analysis of the entire sequence of both patient's mtDNA showed several nucleotide substitutions including alteration of the initiation codon of the NADH dehydrogenase 5 gene. Some of these nucleotide substitutions might contribute to the phenotypic expression of Pearson's syndrome synergistically with the deletion.

Anemia, Sideroblastic↗
PubMed1999

Repopulation of rho0 cells with mitochondria from a patient with a mitochondrial DNA point mutation in tRNA(Gly) results in respiratory chain dysfunction.

Familial hypertrophic ventricular cardiomyopathy has been demonstrated to be associated with a number of mitochondrial DNA (mtDNA) mutations. A fibroblast cell line carrying a mutation in its mtDNA at position 9997 in the gene encoding tRNA glycine was obtained from a patient with hypertrophic cardiomyopathy. To demonstrate that the etiology of this disease was a result of the mtDNA mutation, cybrid clones were constructed by fusion of enucleated patient skin fibroblasts to rho0 osteosarcoma cells. Clones carrying high levels of mutant mtDNA showed predominantly cytochrome c oxidase and complex I deficiency, as well as an elevated lactate/pyruvate (L/P) ratio, a biochemical marker characteristic of respiratory chain deficiencies. Pulse-labeling experiments demonstrated a strong negative correlation between the levels of newly synthesized mtDNA-encoded polypeptides and glycine content. These data suggest that the T9997C mutation in mtDNA is causative of respiratory chain dysfunction when present at high levels of heteroplasmy.

Blotting, Southern↗
PubMed2005

[Distribution of nucleotide substitutions in human mitochondrial DNA genes].

To analyze the distribution pattern of nucleotide substitutions in human mitochondrial DNA (mtDNA), mutational spectra of the mitochondrial genes were reconstructed. The reconstruction procedure is based on the mutation distribution data for 47 monophyletic mtDNA clusters, to which 794 examined mtDNA sequences encoding for tRNAs, rRNAs, and mitochondrial proteins are attributed. One of specific features of mitochondrial mutational spectra revealed was homoplasy of the mutations (the mean mutation number per variable nucleotide site in the coding region varied from 1.09 to 1.43). It was established that in the mtDNA genes maximum mutational constraint fell onto the guanine bases, albeit the content of these bases in the mtDNA L-chains was minimal. Maximal bias towards parallel G to A transitions was observed for rRNA genes, with the protein- and tRNA-encoding genes ranking next. Despite the fact that the differences in the average G-nucleotides content and variability between the genes of two mtDNA segments located between the OriH and OriL were statistically significant, the results did not provide the conclusion that the G-nucleotide instability observed in the mtDNA L-spectra was determined by the mechanism of asynchronous mtDNA replication, along with the deamination of cytosines in the H-chain regions, which remained single-stranded during replication.

DNA, Mitochondrial↗
PubMed1996

Simultaneous increase of mitochondrial DNA deletions and lipid peroxidation in human aging.

Human mtDNA is a naked circular double-stranded DNA, which is continually exposed to the matrix that contains high levels of ROS and free radicals. High oxidative stress and a lack of proofreading during mtDNA replication and efficient DNA repair mechanisms in the mitochondria have rendered mtDNA extremely vulnerable to oxidative damage. More than one dozen large-scale deletions in mtDNA have been identified in various tissues of old humans. The 4,977-bp and 7,436-bp deletions are the most prevalent and abundant ones. The onset age of various mtDNA deletions varies greatly with tissues of each individual and type of deletion. In this and previous studies, we have demonstrated with PCR techniques that the frequency of occurrence and the proportion of the 4,977-bp and 7,436-bp deleted mtDNAs are significantly increased with the age of the human. The mtDNA deletions are not detectable in any tissues from young healthy subjects or blood cells from normal individuals of any age, which indicates that the deletions are generated and accumulated only in postmitotic cells upon aging. Moreover, we found that these mtDNA deletions occur more frequently and abundantly in tissues with high energy demand (e.g., muscle) as compared to those with low energy demand. On the other hand, we found that the amount of lipid peroxides measured as malondialdehyde and the activity of manganese-superoxide dismutase in the mitochondria exhibit an age-dependent increase in various human tissues. The lipid peroxide level in muscle was significantly higher than that in the other tissues. Moreover, we found a positive correlation between the proportion of the 4,977-bp deleted mtDNA and lipid peroxide content in the mitochondria of human tissues during aging. Muscle the tissue of high energy demand, was found to be more vulnerable to oxidative damage that lead to most abundant mtDNA deletions and lipid peroxidation among all the tissues examined. Taking these results together, we suggest that the enhanced generation of reactive oxygen species and lipid peroxides in the mitochondria during the aging process occur simultaneously with large-scale deletions and the other types of mutations in mtDNA, which are early molecular events and major contributory factors of human aging.

Age Distribution↗
PubMed1996

Accumulation of deletions and point mutations in mitochondrial genome in degenerative diseases.

Accumulation of various mutations in the mitochondrial genome is proposed as an important contributor to aging and degenerative diseases. Extensive fragmentation of mtDNA was detected in association with increased 8-hydroxydeoxyguanosine content in the heart mitochondrial DNA (mtDNA) from a patient with premature aging and mitochondrial cardiomyopathy, who carried a mutation within the mitochondrial tRNA(Asp) gene. This result suggests that damage to mtDNA by hydroxyl radical and accumulation of deleted mtDNA can be accelerated by a specific mitochondrial genotype. Similarly, extensive fragmentation of mtDNA was also detected in cultured cells exposed to a high oxygen concentration atmosphere, implying that mtDNA is vulnerable to reactive oxygen species. To clarify the role of point mutations accumulated in mtDNA, we examined the sequence heterogeneity of mtDNA in the skeletal muscle of a MELAS patient who carried a mutation within the mitochondrial tRNA(leu)(UUR) gene. The analysis revealed that the frequency of mutant clones in the MELAS muscle was significantly higher than those in an age-matched control muscle and a control placenta. Some of these nucleotide substitutions were missense and nonsense mutations, which potentially have deleterious effects on the mitochondrial function. The frequency of nucleotide substitutions in the striatum of three patients with Parkinson's disease was also significantly higher than that in control tissues. We also observed increased protein modification by 4-hydroxy-2-nonenal, a lipid peroxidation by-product, in Parkinson's disease. These results suggests that a vicious cycle contributes to the progression of degenerative process. In this cycle, first a primary mitochondrial mutation(s) induces a mitochondrial respiratory defect, which increases the leakage of reactive oxygen species (ROS) from the respiratory chain. Then the ROS would trigger accumulation of secondary mtDNA mutations in postmitotic cells, leading to further aggravation of mitochondrial respiratory defects and increased production of ROS and lipid peroxides from mitochondria, and thus resulting in degeneration of cellular components.

Aged↗
PubMed1997

Cardiac mitochondrial dysfunction and DNA depletion in children with hypertrophic cardiomyopathy.

Abnormalities in specific mitochondrial respiratory enzymes and DNA (mtDNA) have been reported in cardiomyopathy. In this study, we report 4 cases of severe hypertrophic cardiomyopathy (HCM) in which specific cardiac mitochondrial enzyme activity defects were found, including complex I (n = 2), complex III (n = 2), complex IV (n = 2) and complex V (n = 1). Other abnormalities were also noted including a marked depletion of mtDNA (n = 1) and decreased content of subunit 2 of cytochrome c oxidase (n = 1). None of the mtDNA point mutations and common deletions previously found in association with cardiomyopathy were detected in these patients. These data indicate that specific respiratory enzyme activity defects are frequently present in HCM. Also, our finding of a marked depletion of mtDNA in 1 patient suggests that cardiac mtDNA depletion, previously unreported in HCM, needs further examination in order to establish whether it plays a primary role in its pathogenesis.

Cardiomyopathy, Hypertrophic↗
PubMed2001

The complete mitochondrial DNA sequence of the basal hexapod Tetrodontophora bielanensis: evidence for heteroplasmy and tRNA translocations.

We present the complete 15,455-nt mitochondrial DNA sequence of the springtail Tetrodontophora bielanensis (Arthropoda, Hexapoda, Collembola). The gene content is typical of most metazoans, with 13 protein-coding genes (PCGs), 2 genes encoding for ribosomal RNA subunits, and 22 tRNA genes. The nucleotide sequence shows the well-known A+T bias typical of insect mtDNA; its A+T content is lower (72.7%) than that observed in other insect species, but still higher than that in other arthropodan taxa. The bias appears to be uniform across the whole molecule, unlike other insect taxa, which show increased A+T content in the so-called A+T-rich region. However, the bias is slightly higher in the third codon positions of the PCGs (81.4%). Anomalous initiation codons have been observed in the nad2 and the cox1 genes. In the latter, the ATTTAA hexanucleotide is suggested to be involved in the initiation signaling. All tRNAs could be folded into the typical cloverleaf secondary structure, but the tRNA for cysteine appears to be missing the DHU arm. Long tandemly repeated regions (193 nt) were found in the A+T-rich region, which in turn was shown to have the possibility of forming a complex array of secondary structures. One of these structures encompassed the junction between the repeats. The A+T-rich region was also interesting in that it showed heteroplasmy in the number of repeats. Three haplotypes were found, possessing 2, 3, and 4 identical repeats, respectively. The order of protein coding and rRNA genes in the molecule was determined and was identical to that of all insects studied so far. However, two tRNA translocations were found which were unprecedented among Arthropoda. These involved the trnQ, which was found between the rrnS and the A+T-rich region, and the trnS(ucn), which was located between trnM and trnI. A preliminary phylogenetic analysis based on the amino acid sequence of the PCGs failed to find support for the monophyly of Hexapoda.

Animals↗
PubMed2002

[Variation of the mitochondrial genome in the evolution of Drosophila].

The evidence on mitochondrial genome variation and its role in evolution of the genus Drosophila are reviewed. The mitochondrial genome is represented by a circular double-stranded DNA molecule 16 to 19 kb in length. The genome contains no introns involved in recombination. The entire mitochondrial genome can be arbitrarily divided into three parts: (1) protein-coding genes; (2) genes encoding rRNA and tRNA; and (3) the noncoding regulatory region (A + T region). The selective importance of mutations within different mtDNA regions is therefore unequal. In Drosophila, the content of the A + T pairs in mtDNA is extremely low and a pattern of nucleotide substitution is characterized by a low transition/transversion ratio (and a low threshold of mutation saturation). The deletions and duplications are of common occurrence in the mitochondrial genome. However, this genome lacks such characteristic for the nuclear genome aberrations as the inversions and transpositions. The phenomena of introgression and heteroplasmy provide an opportunity to study the adaptive role of the mitochondrial genome and its role in speciation. Analysis of evidence concerning mtDNA variation in different species of the genus Drosophila made it possible to ascertain data on phylogenetic relationships among species obtained by studying nuclear genome variation. In some species, mtDNA variation may serve as a reliable marker for population differentiation within a species, although evidence on the population dynamics of the mtDNA variation is very scarce.

Animals↗
PubMed2001

Increases of mitochondrial mass and mitochondrial genome in association with enhanced oxidative stress in human cells harboring 4,977 BP-deleted mitochondrial DNA.

In order to investigate the effect of aging- and disease-associated deletion of mtDNA on cellular functions, we used cytoplasm fusion to construct a series of the cybrids harboring varying proportions of mtDNA with 4,977 bp deletion from skin fibroblasts of a patient with chronic progressive external ophthalmoplegia. The cybrids were grown in the Dulbecco's modified Eagle medium supplemented with 5% fetal bovine serum, 100 microg/ml pyruvate and 50 microg/ml uridine. The population doubling time was longer for the cybrids containing higher proportions of 4,977 bp-deleted mtDNA. In addition, we found that the respiratory function was decreased with the increase of mtDNA with 4,977 bp deletion in the cybrids. Since impairment of the respiratory system of mitochondria increases the electron leak of the respiratory chain, we further determined the oxidative stress in these cybrids. The results showed that the specific contents of 8-hydroxy 2'-deoxyguanosine and lipid peroxides of the cybrids harboring > 65% of the 4,977 bp-deleted mtDNA were significantly increased as compared with those of the cybrids containing undetectable mutant mtDNA. On the other hand, we found that the mitochondrial mass and the relative content of the mitochondrial genome in the cybrids harboring 4,977 bp-deleted mtDNA were higher than those of the cybrids containing only wild type mtDNA. The relative content of mtDNA was increased 17% and 30%, respectively, in the cybrids harboring 17% and 56% of mtDNA with 4,977 bp deletion. Moreover, both mitochondrial mass and mtDNA content were concurrently increased by treatment of the cybrids with 180 microM of hydrogen peroxide. Taken these findings together, we conclude that increase of mitochondrial mass and mtDNA are the molecular events associated with enhanced oxidative stress in human cells with impaired respiratory function caused by mtDNA deletion.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1977

The structure of animal mitochondrial DNA (base composition, pyrimidine clusters, character of methylation).

Base composition, content of pyrimidine isopliths and the degree of methylation of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) from various vertebrates and protozoon Crithidia oncopelti have been studied. MtDNAs from mammals (ox, rat) do not differ in fact in the GC content from the respective nDNA. The GC content in mtDNA from fishes (sheat fish) and birds (duck, chicken) is 1.5-2.5 mole % higher than in the respective nDNA. Kinetoplast DNA (kDNA) from Crithidia oncopelti (GC = 42.9 mole %) differs significantly in base composition from nDNA (GC = 51.3 mole %). All the mtDNA and kDNA studied differ from the respective nDNA by a lower degree of pyrimidine clustering. The amount of mono and dipyrimidine fragments in mtDNA is more than 30 mole %, whereas in nDNA it does not exceed 23 mole %. The quantity of long pyrimidine clusters (hexa and others) is 2-4 times lower in mtDNA than in nDNA. The lower degree of clustering of pyrimidine nucleotides seems to be a specific feature of all the mtDNA studied. This may be indicative of common traits in the organization and origin of mtDNA. All mtDNA of vertebrates contain 5-methylcytosine as a 'minor' base (1.5- 3.15 mole %) and surpass by 1.5-2 times the respective nDNA in the methylation degree. It has been found that in animals mtDNA is species specific as far as the 5-methyl-cytosine content is concerned. In mitochondria and nuclei of rat liver certain DNA methylase activity has been detected, which provides in vitro the methylation of cytosine residues both in homologous DNA and various heterologous DNAs. The specificity of methylation in vitro of cytosine residues in the same heterologous DNA from E. coli B varies with the source of enzymes. The mitochondrial enzyme methylates cytosine as the lone monopyrimidine residue, whereas the nuclear enzyme methylase cytosine in the di- and tripyrimidine fragments.

Animals↗