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PubMed1993

Multiple symmetric lipomas with high levels of mtDNA with the tRNA(Lys) A-->G(8344) mutation as the only manifestation of disease in a carrier of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome.

We have investigated the morphology, cytogenetics, and the fraction of mtDNA with the tRNA(Lys) A-->G(8344) mutation in three lipomas in a carrier of this mutation. The son of the patient had myoclonus epilepsy and ragged-red fibers syndrome. The fraction of mtDNA with the tRNA(Lys) mutation varied between 62% and 80% in cultured skin fibroblasts, lymphocytes, normal adipose tissue, and muscle. In the three lipomas the mean fraction of mutated mtDNA was 90%, 94%, and 94%. Ultrastructural examination of the lipomas revealed numerous mitochondria with changes such as electron-dense inclusions in some adipocytes. When considered cytogenetically, the lipomas were characterized by a mixture of karyotypically abnormal and normal cells. An identical del(6)(q24) was found in two tumors. The fraction of mutated mtDNA in cultured lipoma cells was the same as in the lipoma in situ, indicating that the cultured cells were representative of the primary tumor. These findings indicate that the lipomas have originated with a grossly normal stem line and subsequently have developed the 6q deletion. We conclude that the lipomas represent clonal growth of adipocytes with a high content of mtDNA with the tRNA(Lys) mutation. The tRNA(Lys) mutation may be either the direct or the indirect cause of pertubation of the maturation process of the adipocytes, leading to an increased risk of lipoma formation.

Adenine↗
PubMed2000

Phylogenetic analysis of diatom coxI genes and implications of a fluctuating GC content on mitochondrial genetic code evolution.

In order to address the relationships among diatom groups and to investigate possible changes in their mitochondrial (mt) genetic codes, we have analyzed a 1.1-kb region of the cytochrome c oxidase subunit I (coxI) gene from eight diverse diatom species. A phylogenetic analysis of these coxI sequences including representative species of the Phaeophyta, Xanthophyta, Eustigmatophyta and Haptophyta showed that the diatoms (Bacillariophyta) formed a well-supported monophyletic group. Of the eight species investigated, four have been classified together as radial centric diatoms based on morphology. However, in our coxI tree, the two radial centrics belonging to the order Thlassiosirales (Skeletonema costatum and Thalassiosira nordenskioldii) were placed as the sister group to the multipolar centric diatoms, while the other two radial centrics (Melosira ambigua and Rhizosolenia setigera) were in another clade. Also, in two species of the Tharassiosirales we found UGA codons that occur at conserved tryptophan (Trp) sites in the coxI sequences, strongly indicating that UGA codes for Trp in these diatoms. No evidence of a deviant genetic code was detected in the other analyzed diatom species. There was no apparent relationship between the nucleotide third-position GC content of mtDNA (based on the sequenced coxI region) and the presence of a deviant genetic code.

Base Composition↗
PubMed1997

Mitochondrial gene expression in rat heart and liver during growth and development.

The levels of mitochondrial enzyme activities involved in respiration and oxidative phosphorylation and of specific mitochondrial gene transcripts were examined in rat heart and liver tissues during early growth, development, and aging. Increases were shown in cardiac respiratory complex activities I, III, IV, and V and ATPase6 and CoxII transcript levels during the transition from neonate to young adult. This increased mitochondrial gene expression is not associated with a proportionate increase in mitochondrial number. In contrast, no significant changes in liver mitochondrial activities or transcripts were detected during this transition. Marked reductions in the activities of complexes I, III, IV, and V and in ATPase6 and COXII transcripts were demonstrated in older adult as compared with young adult cardiac tissue with no concomitant reduction in cardiac citrate synthase activity and content, and mtDNA copy number. No decline was noted in liver mitochondrial enzyme activity levels and transcripts of old adult rats. These findings suggest that cardiac mitochondrial gene expression is developmentally regulated at a pretranslational level. The pattern of increasing mitochondrial gene expression in the young adult and decreasing gene expression in the aging heart stands in clear contrast to liver mitochondrial gene expression or nuclear-encoded genes such as citrate synthase.

Aging↗
PubMed2001

Abnormal cardiac and skeletal muscle mitochondrial function in pacing-induced cardiac failure.

BACKGROUND: Previous studies have shown that marked changes in myocardial mitochondrial structure and function occur in human cardiac failure. To further understand the cellular events and to clarify their role in the pathology of cardiac failure, we have examined mitochondrial enzymatic function and peptide content, and mitochondrial DNA (mtDNA) integrity in a canine model of pacing-induced cardiac failure. METHODS: Myocardium and skeletal muscle tissues were evaluated for levels of respiratory complex I-V and citrate synthase activities, large-scale mtDNA deletions as well as peptide content of specific mitochondrial enzyme subunits. Levels of circulating and cardiac tumor necrosis factor-alpha (TNF-alpha), and of total aldehyde content in left ventricle were also assessed. RESULTS: Specific activity levels of complex III and V were significantly lower in both myocardial and skeletal muscle tissues of paced animals compared to controls. In contrast, activity levels of complex I, II, IV and citrate synthase were unchanged, as was the peptide content of specific mitochondrial enzyme subunits. Large-scale mtDNA deletions were found to be more likely present in myocardial tissue of paced as compared to control animals, albeit at a relatively low proportion of mtDNA molecules (<0.01% of wild-type). In addition, the reduction in complex III and V activities was correlated with elevated plasma and cardiac TNF-alpha levels. Significant increases in left ventricle aldehyde levels were also found. CONCLUSIONS: Our data show reductions in specific mitochondrial respiratory enzyme activities in pacing-induced heart failure which is not likely due to overall decreases in mitochondrial number, or necrosis. Our findings suggest a role for mitochondrial dysfunction in the pathogenesis of cardiac failure and may indicate a commonality in the signaling for pacing-induced mitochondrial dysfunction in myocardial and skeletal muscle. Increased levels of TNF-alpha and oxidative stress appear to play a contributory role.

Adenosine Triphosphatases↗
PubMed2005

Novel mitochondrial gene content and gene arrangement indicate illegitimate inter-mtDNA recombination in the chigger mite, Leptotrombidium pallidum.

To better understand the evolution of mitochondrial (mt) genomes in the Acari (mites and ticks), we sequenced the mt genome of the chigger mite, Leptotrombidium pallidum (Arthropoda: Acari: Acariformes). This genome is highly rearranged relative to that of the hypothetical ancestor of the arthropods and the other species of Acari studied. The mt genome of L. pallidum has two genes for large subunit rRNA, a pseudogene for small subunit rRNA, and four nearly identical large noncoding regions. Nineteen of the 22 tRNAs encoded by this genome apparently lack either a T-arm or a D-arm. Further, the mt genome of L. pallidum has two distantly separated sections with identical sequences but opposite orientations of transcription. This arrangement cannot be accounted for by homologous recombination or by previously known mechanisms of mt gene rearrangement. The most plausible explanation for the origin of this arrangement is illegitimate inter-mtDNA recombination, which has not been reported previously in animals. In light of the evidence from previous experiments on recombination in nuclear and mt genomes of animals, we propose a model of illegitimate inter-mtDNA recombination to account for the novel gene content and gene arrangement in the mt genome of L. pallidum.

Animals↗
PubMed1992

Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts.

Some mutations in mitochondrial DNA (mtDNA) causing a number of neuromuscular diseases are suggested to arise spontaneously during the life of an individual. To substantiate the extent and the rate of these somatic mutations, mtDNA specimens from post-mortem human heart muscles of subjects in differing age groups were hydrolyzed. 8-Hydroxy-deoxyguanosine (8-OH-dG), a hydroxyl-radical adduct of deoxyguanosine, in mtDNA, was quantitatively determined using a micro high-performance liquid chromatography/mass spectrometry system. In each specimen, the mtDNA with a 7.4 kilo base-pair deletion was quantified by the kinetic polymerase chain reaction method. In association with age, the 8-OH-dG content accumulated exponentially up to 1.5% with a correlative increase in the content of the deleted mtDNA up to 7%. Clear correlation between the 8-OH-dG content in mtDNA and the population of mtDNA with a deletion (r = 0.93, P < 0.01) gives insight into the mechanism for the generation of a large deletion. These results indicate that accumulation of somatically acquired oxygen damage together with age-associated mutations in mtDNA which lead to bioenergetic deficiency and the heart muscle weakness are inevitable in human life.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1980

Uniqueness of sperm mtDNA as compared to somatic mtDNA in ram.

Sperm mtDNA exhibits unique physicochemical properties compared with mtDNA from somatic tissues in the ram. The buoyant density of sperm mtDNA was 1,6983 g/cm3 while the brain, heart and liver mtDNAs was about 1.7005 g/cm3. The Tm of the liver and sperm mtDNA was 71.0 degrees C and 69.5 degrees C, respectively. The G + C content of sperm mtDNA was 3.0 moles % lower than the liver mtDNA. The contour length of the circular sperm mtDNA was 5.01 micrometers compared with the liver mtDNA with contour length of 5.33 micrometers.

Animals↗
PubMed2002

The chloroplast and mitochondrial genome sequences of the charophyte Chaetosphaeridium globosum: insights into the timing of the events that restructured organelle DNAs within the green algal lineage that led to land plants.

The land plants and their immediate green algal ancestors, the charophytes, form the Streptophyta. There is evidence that both the chloroplast DNA (cpDNA) and mitochondrial DNA (mtDNA) underwent substantial changes in their architecture (intron insertions, gene losses, scrambling in gene order, and genome expansion in the case of mtDNA) during the evolution of streptophytes; however, because no charophyte organelle DNAs have been sequenced completely thus far, the suite of events that shaped streptophyte organelle genomes remains largely unknown. Here, we have determined the complete cpDNA (131,183 bp) and mtDNA (56,574 bp) sequences of the charophyte Chaetosphaeridium globosum (Coleochaetales). At the levels of gene content (124 genes), intron composition (18 introns), and gene order, Chaetosphaeridium cpDNA is remarkably similar to land-plant cpDNAs, implying that most of the features characteristic of land-plant lineages were gained during the evolution of charophytes. Although the gene content of Chaetosphaeridium mtDNA (67 genes) closely resembles that of the bryophyte Marchantia polymorpha (69 genes), this charophyte mtDNA differs substantially from its land-plant relatives at the levels of size, intron composition (11 introns), and gene order. Our finding that it shares only one intron with its land-plant counterparts supports the idea that the vast majority of mitochondrial introns in land plants appeared after the emergence of these organisms. Our results also suggest that the events accounting for the spacious intergenic spacers found in land-plant mtDNAs took place late during the evolution of charophytes or coincided with the transition from charophytes to land plants.

Biological Evolution↗
PubMed1998

Human mitochondrial function during cardiac growth and development.

Little information is presently available concerning mitochondrial respiratory and oxidative phosphorylation function in the normal human heart during growth and development. We investigated the levels of specific mitochondrial enzyme activities and content during cardiac growth and development from the early neonatal period (10-20 days) to adulthood (67 years). Biochemical analysis of enzyme specific activities and content and mitochondrial DNA (mtDNA) copy number was performed with left ventricular tissues derived from 30 control individuals. The levels of cytochrome c oxidase (COX) and complex V specific activity, mtDNA copy number and COX subunit II content remained unchanged in contrast to increased citrate synthase (CS) activity and content. The developmental increase in CS activity paralleled increasing CS polypeptide content, but was neither related to overall increases in mitochondrial number nor coordinately regulated with mitochondrial respiratory enzyme activities. Our findings of unchanged levels of cardiac mitochondrial respiratory enzyme activity during the progression from early childhood to older adult contrasts with the age-specific regulation found with CS, a Krebs cycle mitochondrial enzyme.

Adenosine Triphosphatases↗
PubMed2001

Molecular analysis of diabetes mellitus-associated A3243G mitochondrial DNA mutation in Taiwanese cases.

Investigation of the clinical manifestations of MELAS-specific A3243G mitochondrial DNA (mtDNA) point mutation has suggested that the A3243G mutation of mtDNA can cause certain subtypes of diabetes mellitus (DM) and contributes about 0.15% of the overall incidence of diabetes. However, a relationship between the diabetic syndrome and the proportion of mutant mtDNA in affected tissues remains unclear. In this article, we report the results of our investigation of 14 diabetic and 23 non-diabetic patients who had the A3243G mutant mtDNA. The proportions of mutant mtDNA in different tissues were noted to change variably and neither heteroplasmy of mutant mtDNA in various tissues nor the proportion of mutated mtDNA in a specific tissue showed a correlation with the clinical phenotype of DM. Generation of a diabetic syndrome was not predictable from either the content of mutant mtDNA in leukocytes, hair follicles, or in muscle tissues. Further study showed that muscle tissue has the highest proportion of mutant mtDNA followed by hair follicles and by blood cells. Moreover, we observed that as the patient's age increased, all tissue showed a declining proportion of mutant mtDNA. These findings suggest that age may play a role in the manifestation of diabetes in patients with A3243G mutation of mtDNA.

Adult↗
PubMed2002

Severe depletion of mitochondrial DNA in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disorder in childhood leading to a dramatic loss of muscle strength. Functional investigations with high-resolution polarography and enzyme measurements of the respiratory chain revealed lowered activities in muscle tissue of SMA patients. To gain a better understanding of this low energy supply we analyzed the amount of mitochondrial DNA (mtDNA) in skeletal muscle of 20 unrelated children with genetically proven SMA and 31 controls. Quantitative Southern blot analysis revealed a severe and homogeneous decrease in the content of muscle mtDNA in relation to nuclear DNA in SMA patients (90.3+/-7.8%), whereas by immunofluorescence no decrease in the number of mitochondria was detected. In addition, a two- to threefold reduction of the nuclear-encoded complex II (succinate dehydrogenase) activity was detected in SMA muscle tissue. Western blot analysis showed a significant reduction of both mitochondrial- and nuclear-encoded cytochrome c oxidase subunits. Our results indicate that mtDNA depletion in SMA is a consequence of severe atrophy, and has to be differentiated by measurement of complex II from an isolated reduction of mtDNA as found in patients with mitochondriocytopathies and the so-called mtDNA depletion syndrome.

Adolescent↗
PubMed1986

An approach to yeast classification by mapping mitochondrial DNA from Dekkera/Brettanomyces and Eeniella genera.

Sequences hybridizing to mitochondrial DNA probes from Saccharomyces cerevisiae have been mapped in six mitochondrial genomes from the Dekkera/Brettanomyces yeasts and in mtDNA from the closely related Eeniella nana. Sequence order for the 34.5 kbp mtDNA of E. nana is identical to that for mtDNAs from B. custersianus (28.5 kbp) and B. naardenensis (41.7 kbp) thereby suggesting that the former yeast is affiliated with the latter two species. A closer relationship is suggested for D. intermedia and D. bruxellensis as mtDNAs from these yeasts, 73.2 and 85.0 kbp respectively, have the same sequence order and mostly common restriction endonuclease sites. Differences between the two molecules are reminiscent of those found in mtDNA polymorphisms of S. cerevisiae strains thereby suggesting that the two Dekkera yeasts are variants of a single species. An unusual feature of the Dekkera species mtDNA is an inversion of the cytochrome b hybridizable region relative to the LrRNA sequence. Likewise mtDNA from B. anomalus (57.7 kbp) has an inversion of the cytochrome oxidase subunit 1 sequence with respect to the LrRNA sequence. By contrast the largest mtDNA (101.1 kbp) from B. custersii has the cytochrome b and LrRNA sequences in the same orientation. In addition hybridizable regions in this mtDNA are found in three clusters that are separated by several thousand base pairs of sequence deficient in restriction endonuclease sites. This observation together with the low guanine and cytosine content of the mtDNA suggests that the regions separating the sequence clusters are mostly adenine and thymine residues.

Chromosome Mapping↗
PubMedDate not supplied

[The presence of mtDNA-like sequences in the DNA of liver chromatin fractions from rats of different ages].

We have used young (2-3 months), adult (6-8 months) and old (26-28 months) rats. Nuclear DNA (nDNA) was isolated from the liver nuclei and chromatin fractions (RCh, repressed chromatin; ACh, transcriptionally active chromatin; MCh, membrane-bound chromatin) and thereafter loaded on nitrocellulose filters. Hybridization was carried out with radioactively labelled mitochondrial DNA (mtDNA) as a probe mtDNA was first isolated from the liver mitochondria of adult rats and then labelled in nick-translation reaction with 32P-dCTP. Radioautography densitometry data have shown that the content of mtDNA-homologous sequences in the liver nDNA was decreased in adult rats (56%) and increased in the old ones (240%), as compared with the young animals. mtDNA-homologous sequences were localized in the young rats mainly in the RCh, while the adult and old rats had similar sequences in the ACh. We suggest that the age-related dynamics of mtDNA-homologous sequences was due to various factors. At the early stages cell differentiation proceeds rapidly and is accompanied by structural and functional reorganization of both nuclear and mitochondrial genomes. These changes increase the probability of contacts and integration of mtDNA fragments and whole molecules in the nuclear genome. As a result, an elevated level of mtDNA-homologous sequences is observed in the liver nuclear genome of young rats. In adult rats, repair and elimination of cells with defective nDNA and decreased proliferation of hepatocytes account for decreased amounts of mtDNA-homologous sequences in nDNA. In old animals, the repair to destruction ratio shifts towards destruction and, hence, mtDNA-homologous sequences are accumulated in the liver nDNA. Age related dynamics of mtDNA-homologous sequences in the liver chromatin fractions is characterized by accumulation of these sequences in ACh and MCh chromatin fractions during maturation and ageing. This also confirms our suggestion that integration of mtDNA-homologous sequences in the nuclear genome is due to various mechanisms operational at the early and late stages of ontogenesis.

Aging↗
PubMed1998

The complete mitochondrial DNA sequence of the rabbit, Oryctolagus cuniculus.

The nucleotide sequence of the complete mitochondrial DNA (mtDNA) molecule of the rabbit (Oryctolagus cuniculus, order Lagomorpha) was determined. The length of the molecule is 17,245 nt, but the length is not absolute due to the presence of different numbers of repeated motifs in the control region. The organization and gene contents of the mtDNA of the rabbit conform to those of other eutherian species. The putative secondary structures of the tRNAs of the rabbit have been described. These structures as well as the structure of the L-strand origin of replication comply with those characteristic for eutherians in general. The compositional differences between the two mtDNA strands have also been detailed.

Animals↗
PubMedDate not supplied

Structure of animal mitochondrial DNA: nucleotide composition, pyrimidine clusters, and methylation character.

The nucleotide composition, relative concentration of pyrimidine clusters, and the degree of methylation of the mitochondrial and nuclear DNA's of various vertebrates and the protozoan Crithidia oncopelti have been studied. With respect to the relative concentration of GC pairs, the mtDNA of animals (bull, rat) does not differ from the corresponding nDNA. The relative concentration of GC pairs in the mtDNA of certain fish and birds is 1.5-2.5 mole% higher than in the respective nDNA. The kinetoplast DNA of the protozoan C. oncopelti (where the relative concentration of the GC pairs is 42.9 mole %) differs very sharply in composition from the nDNA (where the relative concentration of GC pairs is 51.3 mole %). The mtDNA's and kDNA's studied are distinguished from the respective nDNA'S by a lower degree of clustering of pyrimidine nucleotides. The proportion of mono- and dipyrimidine fragments in the mtDNA and kDNA is 30 mole %, while in the nDNA it does not exceed 23 mole %. The relative concentration of long pyrimidine clusters (hexapyrimidine clusters of larger) in the mtDNA is smaller than in the nDNA by a factor of 2-5. The low degree of clustering of the pyrimidine nucleotides is apparently characteristic of all the known mtDNA's and may support the fact that they have a single type of organization and are of a single origin. All the vertebrate mtDNA's studied contain 5-methylcytosine as a minor base (1.5-3.15 mole %), and their level of methylation is 1.5-2 times greater than that in the respective nDNA's. It has been shown that animals display species specificity with respect to the 5-methylcytosine content in the mtDNA. Its distribution among the pyrimidine clusters in the bovine heart mtDNA differs substantially from that in the nDNA. This suggests that the methylation specificities of nuclear and mitochondrial DNA are different. A DNA methylase, which effects the in vitro methylation of cytosine residues both in the homologous mtDNA and in different heterologous DNA's, has been found in rat liver and bovine heart mitochondria. The specificity of the in vitro methylation of the cytosine residues in the same heterologous Escherichia coli B DNA by the nuclear and mitochondrial enzymes is different: The mitochondrial enzyme methylates predominantly in monopyrimidine fragments, and the nuclear enzyme methylates mostly in di- and tripyrimidine fragments. They, therefore, recognize different nucleotide sequences.

Animals↗
PubMed2004

Genetic and functional analysis of mitochondrial DNA-encoded complex I genes.

Mammalian mitochondrial NADH dehydrogenase (complex I) is a multimeric complex consisting of at least 45 subunits, 7 of which are encoded by mitochondrial DNA (mtDNA). The function of these subunits is largely unknown. We have established an efficient method to isolate and characterize cells carrying mutations in various mtDNA-encoded complex I genes. With this method, 15 mouse cell lines with deficiencies in complex I-dependent respiration were obtained, and two near-homoplasmic mutations in mouse ND5 and ND6 genes were isolated. Furthermore, by generating a series of cell lines with the same nuclear background but different content of an mtDNA nonsense mutation, we analyzed the genetic and functional thresholds in mouse mitochondria. We found that in wild-type cells, about 40% of ND5 mRNA is in excess of that required to support a normal rate of ND5 subunit synthesis. However, there is no indication of compensatory upsurge in either transcription or translation with the increase in the proportion of mutant ND5 genes. Interestingly, the highest ND5 protein synthesis rate was just sufficient to support the maximum complex I-dependent respiration rate, suggesting a tight regulation at the translational level. In another line of research, we showed that the mitochondrial NADH-quinone oxidoreductase of Saccharomyces cerevisiae (NDI1), although consisting of a single subunit, can completely restore respiratory NADH dehydrogenase activity in mutant human cells that lack the essential mtDNA-encoded subunit ND4. In particular, in these transfected cells, the yeast enzyme becomes integrated into the human respiratory chain and fully restores the capacity of the cells to grow in galactose medium.

Animals↗
PubMed1996

Skeletal muscle mitochondria from AZT-treated rats have a diminished response to chronic electrical stimulation.

Inhibition of DNA polymerase gamma-function mediated by 3'-azido-3'-deoxythymidine (AZT) has been proposed to cause a myopathy by reducing mitochondrial DNA (mtDNA) replication. Repeated bouts of exercise stimulate an increase in mtDNA replication, mitochondrial content, and mitochondrial volume fraction. Therefore, adaptation of rat skeletal muscle [tibialis anterior (TA)] mitochondria exposed to AZT (1 mg/ml for 35 days) and then to electrical stimulation for 8 h/day (7, 14, 21 days) with continued AZT treatment was examined. Fourteen and 21 days of stimulation increased TA cytochrome oxidase (CO) activity, mtDNA, and CO subunit III and VIc mRNA levels in both groups. The TA CO activity and CO III mRNA increases after 14 and 21 days of stimulation were diminished in AZT-treated rats. TA glyceraldehyde-3-phosphate dehydrogenase was reduced in normal rats after chronic stimulation but was unchanged in AZT-treated rats. Chronic stimulation increased the mitochondrial volume fraction by 80 and 40% in normal and AZT-treated rats, respectively. These results indicate diminution, but not complete inhibition, of mitochondrial adaptation by AZT-treated skeletal muscle in response to stimulation.

Animals↗
PubMed1986

Effects of normal human fibroblast mitochondrial DNA on segregation of HeLaTG Mitochondrial DNA and on tumorigenicity of HeLaTG cells.

We isolated hybrids and cybrids using HeLaTG cells and human normal primary fibroblasts to examine the functional differences between the mitochondrial genomes of tumor and normal cells with respect to their possible involvement in the regulation of tumorigenicity. Hybrids contained mitochondrial DNA (mtDNA) predominantly from the fibroblast parent and their tumorigenicity was suppressed completely. Then, cytoplasmic transmission of primary fibroblast mtDNA to HeLaTG cells was carried out using toxin-antitoxin selection. Two cybrid clones containing a HeLaTG nucleus only and more than 60% of transmitted fibroblast mtDNA were isolated and injected into nude mice to test their tumorigenicity. They formed tumors when 2 X 10(6) cells were injected, whereas no tumors were formed after injection of 5 X 10(5) cells (a concentration at which HeLaTG subclones formed tumors). These cybrids were cultivated in normal medium for two additional months and the content of fibroblast mtDNA increased gradually, resulting in HeLaTG mtDNA eventually being lost from both cybrid clones. We again examined their tumorigenicity and found that they recovered tumorigenicity completely. These results indicate that tumorigenicity of HeLaTG cells could not be suppressed by replacing their mitochondrial genomes with those of normal primary fibroblasts. Further, the partial suppression of tumorigenicity observed in the cybrid clones was temporary and may be due to cytoplasmic factors other than the mitochondrial genomes. Although we can find no difference between the mitochondrial genomes of normal and tumor cells regarding the regulation of tumorigenicity, the segregation pattern of the mtDNA in the cybrids was of interest: in the absence of any mitochondrial selection, HeLaTG mtDNA was lost while fibroblast mtDNA was retained, even though the nuclear component of these cybrids was from the HeLaTG cells. Thus, there should be some functional differences between the mitochondrial genomes of HeLaTG cells and primary fibroblasts that are responsible for the preferential segregation of HeLaTG mtDNA from the cybrids.

Animals↗