Mitochondrial DNA haplotypes from the displacement-loop (D-loop) region (436 bp) were genotyped and sequenced in Japanese Black beef cattle raised in the same herd. Correlation coefficients between mitochondrial DNA haplotypes, maternal lineage, birth weight, preweaning average daily gain, weaning weight, post weaning average daily gain and yearling weight were computed. The objective was to study the relationship between maternal and postnatal growth traits and to investigate if postnatal growth of calves to yearling age could be accurately predicted from mitochondrial DNA haplotypes. Results of the phylogenetic analysis revealed 17 maternal lineages and four mitochondrial DNA haplotypes. There were strong, positive and highly significant (p,0.001) correlations among maternal traits ranging from 0.52 to 0.98. Similarly, among postnatal growth traits, most of the correlations were also strong, positive and highly significant (p,0.001); the highest correlation of 0.94 was between preweaning ...
Objective Using real-time fluorescence quantitative PCR to detect mitochondrial DNA content changes within HepG2 cells induced by d4T and AZT. Methods HepG2 cells were treated with different concentrations(0,3,10,100,200,300μmol/L) of d4T and AZT respectively for two weeks. And then mitochondrial DNA contents were detected by real-time fluorescence quantitative PCR. Results Real-time fluorescence quantitative PCR was set up successfully to detect mitochondrial DNA contents. Mitochondrial DNA relative amounts were 96.94±5.77, 53.73±7.14, 20.78±3.10, 1.37±0.29 respectively with d4T concentrations of 0, 3, 10, 100μmol/L. The differences between groups were significant(P0.01). However, they were 96.94±5.77, 108.84±7.80, 172.56±4.70, 199.51±10.37, 158.74±6.64 and 64.06±6.27 respectively with AZT concentrations of 0, 3, 10, 100, 200, 300μmol/L, and the differences between groups were significant(P0.01). Conclusions It is practicable to detect mitochondrial DNA contents with real-time fluorescence
Exciting new studies are increasingly strengthening the link between mitochondrial mutagenesis and tumor progression. Here we provide a comprehensive review and meta-analysis of studies reporting on mitochondrial DNA mutations in common human cancers. We discuss possible mechanisms by which mitochondrial DNA mutations may influence carcinogenesis, outline important caveats for interpreting the detected mutations--particularly differentiating causality from association--and suggest how new mutational assays may help resolve fundamental controversies in the field and delineate the origin and expansion of neoplastic cell lineages. Finally, we discuss the potential clinical utility of mtDNA mutations for improving the sensitivity of early cancer diagnosis, rapidly detecting cancer recurrence, and predicting the disease outcome.. ...
From previous studies, it is known that the low OA risk haplogroup J is associated with lower serum levels of markers of collagen type-II degradation and of matrix metalloproteinases, but all of these studies failed to address the key question arising from this large body of evidence: What is the functional role of these mtDNA haplogroups?. To answer this question, Fernandez-Moreno et al7 used cytoplasmic hybrid (cybrid) cell lines. Cybrids incorporate mitochondria from human subjects and perpetuate the mtDNA-encoded components while maintaining the nuclear background of different cybrid lines as constant.16 Thus, this technique allows investigators to assess the influence of mtDNA variation on cell function. To investigate the role of mtDNA haplogroups, they also created cybrids using osteosarcoma cell lines with the same nuclear background, one of them harbouring the haplogroup J (which protects against OA) and another harbouring the haplogroup H (linked to higher risk of OA).. The cybrids ...
Saeidi, Z., Rezvani Gilkolaei, S., Soltani, M. (2017). Short communication: Population genetic structure studies of Liza aurata based on mtDNA control region sequences analyses in the southern coasts of the Caspian Sea, Iranian Journal of Fisheries Sciences, 17(4), pp. 1341-1348. doi: 10.22092/ijfs. ...
Mitochondrial DNA (mtDNA) heteroplasmy is a potential genetic marker for forensic mtDNA analysis as well as phylogenic studies. Frequency of mtDNA …
TY - JOUR. T1 - Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. AU - Kang, Eunju. AU - Wu, Jun. AU - Gutierrez, Nuria Marti. AU - Koski, Amy. AU - Tippner-Hedges, Rebecca. AU - Agaronyan, Karen. AU - Platero-Luengo, Aida. AU - Martinez-Redondo, Paloma. AU - Ma, Hong. AU - Lee, Yeonmi. AU - Hayama, Tomonari. AU - Van Dyken, Crystal. AU - Wang, Xinjian. AU - Luo, Shiyu. AU - Ahmed, Riffat. AU - Li, Ying. AU - Ji, Dongmei. AU - Kayali, Refik. AU - Cinnioglu, Cengiz. AU - Olson, Susan. AU - Jensen, Jeffrey. AU - Battaglia, David. AU - Lee, David. AU - Wu, Diana. AU - Huang, Taosheng. AU - Wolf, Don P.. AU - Temiakov, Dmitry. AU - Belmonte, Juan Carlos Izpisua. AU - Amato, Paula. AU - Mitalipov, Shoukhrat. PY - 2016/12/8. Y1 - 2016/12/8. N2 - Maternally inherited mitochondrial (mt)DNA mutations can cause fatal or severely debilitating syndromes in children, with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type ...
Genetic Relationships of Cattle Breeds Assessed by PCR-RFLP of the Bovine Mitochondrial DNA D-loop Region - Bos Taurus;Bos Indicus;Mitochondrial DNA;PCR-RFLP;Genetic Distance;
The present invention provides methods for rapid forensic analysis of mitochondrial DNA and methods for characterizing heteroplasmy of mitochondrial DNA, which can be used to assess the progression of mitochondrial diseases.
Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C | T and A | G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational
Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, adenosine triphosphate (ATP). Mitochondrial DNA is only a small portion of the DNA in a eukaryotic cell; most of the DNA can be found in the cell nucleus and, in plants and algae, also in plastids such as chloroplasts. In humans, the 16,569 base pairs of mitochondrial DNA encode for only 37 genes. Human mitochondrial DNA was the first significant part of the human genome to be sequenced. In most species, including humans, mtDNA is inherited solely from the mother. Since animal mtDNA evolves faster than nuclear genetic markers, it represents a mainstay of phylogenetics and evolutionary biology. It also permits an examination of the relatedness of populations, and so has become important in anthropology and biogeography. Nuclear and mitochondrial DNA are thought to be of separate evolutionary origin, with the mtDNA ...
Mitochondrial dysfunction, generally characterized as a loss of efficiency in oxidative phosphorylation, is a hallmark of aging and a variety of chronic diseases. Mitochondrial dysfunction results in inefficient cellular energy production and in increased levels of reactive oxygen species (ROS) which may damage lipids, proteins, and nucleic acids. Mitochondrial dysfunction also affects the expression of nuclear genes involved in metabolism, growth, differentiation, and apoptosis. All these changes may explain the contribution of mitochondrial dysfunction to chronic and complex human diseases. A major limitation to the routine evaluation of mitochondrial dysfunction in clinical practice is the lack of reliable measures of mitochondrial dysfunction available for clinical use. Mitochondrial DNA copy number (mtDNA-CN) is a promising biomarker of mitochondrial dysfunction that has the potential to become widely available in clinical practice. Other measures of mitochondrial dysfunction, including ...
Although highly active antiretroviral therapy (HAART) has been extremely effective in lowering AIDS incidence among patients infected with HIV, certain drugs included in HAART can cause serious mitochondrial toxicities. One of the most frequent adverse events is lipoatrophy, which is the loss of subcutaneous fat in the face, arms, buttocks, and/or legs as an adverse reaction to nucleoside reverse transcriptase inhibitors. The clinical symptoms of lipoatrophy resemble those of inherited mitochondrial diseases, which suggest that host mitochondrial genotype may play a role in susceptibility. We analyzed the association between mitochondrial haplogroup and severity of lipoatrophy in HIV-infected European American patients on HAART in the Multicenter AIDS cohort Study and found that mitochondrial haplogroup H was strongly associated with increased atrophy [arms: P = 0.007, odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.17 to 2.69; legs: P = 0.037, OR = 1.54, 95% CI = 1.03 to 2.31; and ...
TY - JOUR. T1 - Alterations of mitochondrial DNA in common diseases and disease states. T2 - Aging, neurodegeneration, heart failure, diabetes and cancer. AU - Kang, Dongchon. AU - Hamasaki, Naotaka. PY - 2005/1/1. Y1 - 2005/1/1. N2 - It has long been considered that mitochondrial DNA disease is a rare genetic disorder causing neuromyopathy. However, alterations of mitochondrial DNA recently have been recognized to play an important role in the pathogenesis of so-called common diseases such as heart failure, diabetes, and cancer. Although some of these alterations are inherited, more and more attention is being focused on the accumulation of mitochondrial DNA mutations in somatic cells, particularly terminally differentiated cells such as cardiomyocytes and neurons that occurs with age. Mitochondrial DNA is more vulnerable to alteration than nuclear DNA, mainly for two reasons. First, mitochondria are a major source of intracellular reactive oxygen species (ROS). Therefore mitochondrial DNA is ...
We had previously found that 6-month survival in sepsis patients was significantly associated with platelet COX quantity [4]. However, 1-month survival is a more frequently used parameter in critically ill patients; and we have found that this parameter is also significantly associated with platelet COX quantity. We had previously observed that COX levels can be determined by mtDNA genetic background [6], and other investigators showed that mtDNA haplogroups modified 6-month survival [9]. Here we show that the mtDNA haplogroup determines the platelet COX quantity in sepsis patients and that those patients from the JT mtDNA haplogroup had higher survival rate than those from other mtDNA haplogroups.. The JT mtDNA haplogroup is defined by polymorphisms in nucleotide positions m.4216T , C/MT-ND1, m.11251A , G/MT-ND4, m.15452C , A/MT-CYB and m.16126T , C/MT-DLOOP. The last polymorphism is located in the control region, out of any important sequence for the regulation of mtDNA replication and ...
We have analyzed nucleotide sequence variation in an approximately 900-base pair region of the human mitochondrial DNA molecule encompassing the heavy strand origin of replication and the D-loop. Our analysis has focused on nucleotide sequences available from seven humans. Average nucleotide diversity among the sequences is 1.7%, several-fold higher than estimates from restriction endonuclease site variation in mtDNA from these individuals and previously reported for other humans. This disparity is consistent with the rapidly evolving nature of this noncoding region. However, several instances of convergent or parallel gain and loss of restriction sites due to multiple substitutions were observed. In addition, other results suggest that restriction site (as well as pairwise sequence) comparisons may underestimate the total number of substitutions that have occurred since the divergence of two mtDNA sequences from a common ancestral sequence, even at low levels of divergence. This emphasizes the ...
To construct maternal phylogeny and prehistoric dispersals of modern human being in the Indian sub continent, a diverse subset of 641 complete mitochondrial DNA (mtDNA) genomes belonging to macrohaplogroup M was chosen from a total collection of 2,783 control-region sequences, sampled from 26 selected tribal populations of India. On the basis of complete mtDNA sequencing, we identified 12 new haplogroups - M53 to M64; redefined/ascertained and characterized haplogroups M2, M3, M4, M5, M6, M8′C′Z, M9, M10, M11, M12-G, D, M18, M30, M33, M35, M37, M38, M39, M40, M41, M43, M45 and M49, which were previously described by control and/or coding-region polymorphisms. Our results indicate that the mtDNA lineages reported in the present study (except East Asian lineages M8′C′Z, M9, M10, M11, M12-G, D ) are restricted to Indian region.The deep rooted lineages of macrohaplogroup M suggest in-situ origin of these haplogroups in India. Most of these deep rooting lineages are represented by multiple ...
Abstract Genetic studies of the distribution of mitochondrial DNA (mtDNA) haplogroups in human populations residing within the Carpathian Mountain range have been scarce. We present an analysis of mtDNA haplogroup composition of the Boykos, Hutsuls, and Lemkos, three population groups of the Carpathian highlands. In our study Hutsuls had the highest frequency of subhaplogroup H1 in central and eastern Europe. Lemkos shared the highest frequency of haplogroup I ever reported and the highest frequency of haplogroup M* in the region. MtDNA haplogroup frequencies in Boykos were different from most modern European populations. We interpreted these unique mtDNA frequencies to be evidence of diverse and dynamic population histories in the Carpathian highland region. ...
article{39c3420c-566c-4f24-879b-c3929d10ccd7, abstract = {It has been suggested that mitochondrial dysfunction and DNA damage are involved in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a compensatory mechanism of mitochondrial dysfunction previously has been associated with B-cell lymphomas, in particular chronic lymphocytic leukemia (CLL). However, current evidence is limited and based on a relatively small number of cases. Using a nested case-control study, we extended these findings with a focus on subtype specific analyses. Relative mtDNA copy number was measured in the buffy coat of prospectively collected blood of 469 lymphoma cases and 469 matched controls. The association between mtDNA copy number and the risk of developing lymphoma and histologic subtypes was examined using logistic regression models. We found no overall association between mtDNA and risk of lymphoma. Subtype analyses revealed, significant increased risks of CLL (n=102) with increasing mtDNA ...
Nutrition during early childhood is linked to metabolic programming. We hypothesized that breastfeeding has long-term consequences on the energy metabolism exemplified by mitochondrial DNA (mtDNA). As part of the third cycle of the Flemish Environment and Health Study (FLEHSIII) cohort, 303 adolescents aged 14-15 years were included. We associated breastfeeding and blood mtDNA content 14-15 years later while adjusting for confounding variables. Compared with non-breastfed adolescents, mtDNA content was 23.1% (95%CI: 4.4-45.2; p = 0.013) higher in breastfed adolescents. Being breastfed for 1-10 weeks, 11-20 weeks, and |20 weeks, was associated with a higher mtDNA content of respectively 16.0% (95%CI: −7.1-44.9; p = 0.191), 23.5% (95%CI: 0.8-51.3; p = 0.042), and 31.5% (95%CI: 4.3-65.7; p = 0.021). Our study showed a positive association between breastfeeding and mtDNA content in adolescents which gradually increased with longer periods of breastfeeding. Higher mtDNA content may be an underlying
Haplogroup L1 is believed to have appeared approximately 110,000 to 170,000 years ago.[citation needed] Haplogroup L1 is a daughter of L1-6 and genetic marker changes are 3666, 7055, 7389, 13789, 14178 and 14560. Although it is typically used to denote a group of lineages found within Africa, L1 is sometimes referred to as haplogroup L1-6. The latter is the macrohaplogroup that includes the majority of Africa-based clades and all haplogroups centered outside of the continent. Haplogroup L1-6 is the macrohaplogroup that includes subclades L1, L2, L4, L5, L6, and also L3, which gave rise to the two non-African haplogroups M and N. Haplogroup L1-6 and its only sibling haplogroup L0 are united by the matrilineal most recent common ancestor, (MRCA) of all living humans, Mitochondrial Eve. The existence of these two lineages, implies that Mitochondrial Eve had at least two daughters, one of whom is the maternal common ancestor of haplogroup L1-6 lineages.[citation needed] ...
The study presents South American mitochondrial DNA (mtDNA) data from selected north (N = 98), central (N = 193) and south (N = 47) Argentinean populations. Sequence analysis of the complete mtDNA con
During the last few years, mitochondrial DNA has attained much attention as a modulator of immune responses. Due to common evolutionary origin, mitochondrial DNA shares various characteristic features with DNA of bacteria, as it consists of a remarkable number of unmethylated DNA as 2′-deoxyribose cytidine-phosphate-guanosine (CpG) islands. Due to this particular feature, mitochondrial DNA seems to be recognized as a pathogen-associated molecular pattern by the innate immune system. Under the normal physiological situation, mitochondrial DNA is enclosed in the double membrane structure of mitochondria. However, upon pathological conditions, it is usually released into the cytoplasm. Growing evidence suggests that this cytosolic mitochondrial DNA induces various innate immune signaling pathways involving NLRP3, toll-like receptor 9, and stimulator of interferon genes (STING) signaling, which participate in triggering downstream cascade and stimulating to produce effector molecules. Mitochondrial DNA is
Holyoake, A. J., McHugh, Patrick C, Wu, M., OCarroll, S., Benny, P., Sin, I. L. and Sin, F. Y. T. (2002) Research of single mitochondrial nucleotide substitutions in male infertility should consider human mitochondrial haplogroups - Reply. International Journal of Andrology, 25 (6). p. 374. ISSN 0105-6263 Metadata only available from this repository ...
Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from
Sharma et al. BMC Genetics (2015) 16:73 DOI 10.1186/s12863-015-0221-0. ^BMC Genetics. RESEARCH ARTICLE. Open Access. Genetic diversity and relationship of Indian cattle inferred from microsatellite and mitochondrial DNA markers. CrossMark. Rekha Sharma , Amit Kishore, Manishi Mukesh, Sonika Ahlawat, Avishek Maitra, Ashwni Kumar Pandey and Madhu Sudan Tantia. Abstract. Background: Indian agriculture is an economic symbiosis of crop and livestock production with cattle as the foundation. Sadly, the population of indigenous cattle (Bos indicus) is declining (8.94 % in last decade) and needs immediate scientific management. Genetic characterization is the first step in the development of proper management strategies for preserving genetic diversity and preventing undesirable loss of alleles. Thus, in this study we investigated genetic diversity and relationship among eleven Indian cattle breeds using 21 microsatellite markers and mitochondrial D loop sequence.. Results: The analysis of autosomal DNA ...
The mitochondrial genome is maternally inherited and harbors 37 genes in a circular molecule of approximately 16.6 kb that is present in hundreds to thousands of copies per cell [1] and has accumulated mutations at a rate at least an order of magnitude higher than its nuclear counterpart [2, 3]. Frequently, more than one mtDNA variant is present in the same individual, a phenomenon called heteroplasmy [4]. The mitochondrial genome is implicated in hundreds of diseases (over 200 catalogued at [5] as of mid-2010) with the majority of them caused by point mutations [6]. Multiple mtDNA mutations might also predispose one to common metabolic and neurological diseases of advanced age, such as diabetes as well as Parkinsons and Alzheimers diseases [7]. Additionally, mtDNA mutations appear to have a role in cancer etiology [8]. Many disease-causing mtDNA variants are heteroplasmic and their clinical manifestation depends on the relative proportion of mutant versus normal mitochondrial genomes [7, 9, ...
Mutations in genes encoding components of the mitochondrial DNA (mtDNA) replication machinery cause mtDNA depletion syndromes (MDSs), which associate ocular features with severe neurological syndromes. Here, we identified heterozygous missense mutations in single-strand binding protein 1 (SSBP1) in 5 unrelated families, leading to the R38Q and R107Q amino acid changes in the mitochondrial single-stranded DNA-binding protein, a crucial protein involved in mtDNA replication. All affected individuals presented optic atrophy, associated with foveopathy in half of the cases. To uncover the structural features underlying SSBP1 mutations, we determined a revised SSBP1 crystal structure. Structural analysis suggested that both mutations affect dimer interactions and presumably distort the DNA-binding region. Using patient fibroblasts, we validated that the R38Q variant destabilizes SSBP1 dimer/tetramer formation, affects mtDNA replication, and induces mtDNA depletion. Our study showing that mutations in ...
The mitochondrial DNA (mtDNA) is highly variable, containing large numbers of pathogenic mutations and neutral polymorphisms. The spectrum of homoplasmic mtDNA variation was characterized in 730 subjects and compared with known pathogenic sites. The frequency and distribution of variants in protein coding genes were inversely correlated with conservation at the amino acid level. Analysis of tRNA secondary structures indicated a preference of variants for the loops and some acceptor stem positions. This comprehensive overview of mtDNA variants distinguishes between regions and positions which are likely not critical, mainly conserved regions with pathogenic mutations and essential regions containing no mutations at all. ...
In this large prospective study of a general population of Northern European descent, no evidence was found for consistent and robust associations between mitochondrial haplogroups and risk of ischemic cardiovascular disease, morbidity from other causes, or mortality. In contrast, several smaller case-control studies have shown associations between mitochondrial haplogroups and myocardial infarction, cerebral infarction, cancer, diabetes mellitus, and neurodegenerative diseases.18-36. The Asian N9b haplogroup (defined by polymorphisms at positions mt5147 and mt16519) has been reported to protect against myocardial infarction in Japanese men (odds ratio [95% CI], 0.2 [0.1 to 0.5]; 920 cases/522 controls) but not in Japanese women (695 cases/434 controls).19 It has been speculated that this reduction in risk of myocardial infarction could be due to a reduction in the production of superoxide and other reactive oxygen species associated with this particular haplogroup19 that thus might confer ...
Endometrial carcinoma is the most commonly diagnosed gynaecological cancer in developed countries. Although the molecular genetics of this disease has been in the focus of many research laboratories for the last 20 years, relevant prognostic and diagnostic markers are still missing. At the same time mitochondrial DNA mutations have been reported in many types of cancer during the last two decades. It is therefore very likely that the mitochondrial genotype is one of the cancer susceptibility factors. To investigate the presence of mtDNA somatic mutations and distribution of inherited polymorphisms in endometrial adenocarcinoma patients we analyzed the D-loop sequence of cancer samples and their corresponding normal tissues and moreover performed mitochondrial haplogroup analysis. We detected 2 somatic mutation and increased incidence of mtDNA polymorphisms, in particular 16223C (80% patients, p = 0.005), 16126C (23%, p = 0.025) and 207A (19%, p = 0.027). Subsequent statistical analysis revealed that
Three pairs of parental (ρ+) and established mitochondrial DNA depleted (ρ0) cells, derived from bone, lung and muscle were used to verify the influence of the nuclear background and the lack of efficient mitochondrial respiratory chain on antioxidant defences and homeostasis of intracellular reactive oxygen species (ROS). Mitochondrial DNA depletion significantly lowered glutathione reductase activity, glutathione (GSH) content, and consistently altered the GSH2 : oxidized glutathione ratio in all of the ρ0 cell lines, albeit to differing extents, indicating the most oxidized redox state in bone ρ0 cells. Activity, as well as gene expression and protein content, of superoxide dismutase showed a decrease in bone and muscle ρ0 cell lines but not in lung ρ0 cells. GSH peroxidase activity was four times higher in all three ρ0 cell lines in comparison to the parental ρ+, suggesting that this may be a necessary adaptation for survival without a functional respiratory chain. Taken together, ...
The mitochondrial DNA (mtDNA) depletion syndrome is a genetically heterogeneous group of diseases caused by nuclear gene mutations and secondary reduction in mtDNA copy number. We describe a patient with progressive muscle weakness and increased creatine kinase and lactate levels. Muscle weakness was first noted at age 1.5 years and he died of respiratory failure and bronchopneumonia at age 3.5 years. The muscle biopsy showed dystrophic features with ragged red fibers and numerous cytochrome c oxidase (COX)-negative fibers. qPCR analysis demonstrated depletion of mtDNA and sequence analysis of the mitochondrial thymidine kinase 2 (TK2) gene revealed two novel heterozygous variants, c.332C , T, p.(T111I) and c.156 + 5G , C. Quantitative analysis of mtDNA in single muscle fibers demonstrated that COX-deficient fibers showed more pronounced depletion of mtDNA when compared with fibers with residual COX activity (P , 0.01, n = 25). There was no evidence of manifestations from other organs than ...
This research involved studying mitochondrial DNA stability using Saccharomyces cerevisiae as a model organism. Gene knockout strains focused on the genes FIS1, DNM1, CLU1 and RTG1. Both FIS1 and DNM1 are involved in mitochondrial fission. The CLU1 gene encodes a protein that may associate with the core complex of eukaryotic translation initiation factor 3 (eIF3) in Saccharomyces cerevisiae. The eIF3 plays a role in initiation of mRNA translation. The specific function of the Clu1p in this process is undefined. The gene knockout of CLU1 does not affect growth or translation initiation. The knockout does however cause defects in mitochondrial distribution and organization. The RTG1 gene encodes a transcription factor (bHLH) involved in interorganelle communication. The protein also contributes to communication between mitochondria, peroxisomes, and the nucleus. Deletion strains of all four genes were studied for spontaneous respiration loss. This assay reveals if certain nuclear gene products have a role
in Evolutionary Applications (2014), 7(6), 645-662. Many reintroduction projects for conservation fail, and there are a large number of factors that may contribute to failure. Genetic analysis can be used to help stack the odds of a reintroduction in ... [more ▼]. Many reintroduction projects for conservation fail, and there are a large number of factors that may contribute to failure. Genetic analysis can be used to help stack the odds of a reintroduction in favour of success, by conducting assessment of source populations to evaluate the possibility of inbreeding and outbreeding depression and by conducting postrelease monitoring. In this study, we use a panel of 306 SNP (single nucleotide polymorphism) markers and 487-489 base pairs of mitochondrial DNA control region sequence data to examine 321 individuals from possible source populations of the Eurasian beaver for a reintroduction to Scotland. We use this information to reassess the phylogenetic history of the Eurasian beavers, to ...
Mitochondrial DNA (mtDNA or mDNA) is the DNA in mitochondria.[1] It is inherited only from mothers, though there are a few rare exceptions. Mitochondria are cellular organelles in eukaryotic cells. They convert chemical energy from food into a form that cells can use, adenosine triphosphate (ATP). Mitochondrial DNA is only a small part of the DNA in a eukaryotic cell. Most of the DNA is in the cell nucleus on chromosomes. In plants, the chloroplasts have DNA as well. In humans, mitochondrial DNA codes for 37 genes and with about 16,600 base pairs in a circle. Human mitochondrial DNA was the first significant part of the human genome to be sequenced. The mtDNA in plants is much larger: Arabidopsis has 367 kilobytes. ...
The physiological roles of the mitochondrial transcription termination factor (mTERF) family are poorly understood. MTERF and its homologues influence transcriptional readthrough in vitro, but the extent to which they regulate mitochondrial RNA levels in vivo is unclear. In addition, MTERF was previously shown to promote replication pausing. To test their roles in mtDNA metabolism, we created cell-lines inducibly expressing epitope-tagged versions of two members of the mTERF family, MTERFD1 and MTERFD3, as well as shRNA constructs targeted at each. We confirmed mitochondrial targeting and lack of sequence-specific DNA binding for both factors. Over-expression of epitope-tagged MTERFD1 or MTERFD3 resulted in modest mtDNA copy-number depletion and an accumulation of specific mtDNA replication intermediates indicating an impairment of the terminal steps of replication. These findings further implicate the mTERF family in restraining replication fork progression and support the idea that they ...
In contrast to the ΔPaAnt allele, the three mutant alleles were viable but responsible for several detrimental effects on vegetative and sexual development, independently of the rmp1 allele. These defects were more pronounced in the PaAntS296M mutant than in PaAntM106P and PaAntA121P. A reduced concentration of the mutant ANT protein was observed in the PaAntM106P and PaAntA121P strains. This could be due to a reduced import efficiency (De Marcos Lousa et al. 2002) or to a reduced stability of the mutant proteins. However, it seems unlikely that this reduction is responsible for the defects observed in the mutants since the mutations are dominant and the deletion of PaAnt is recessive (not shown) as is the deletion of AAC2 in S. cerevisiae (Chen 2004). This strongly suggests that the mutant phenotypes are due to an alteration of, and not to a decreased amount of, mutant proteins.. In humans, the three adPEO mutations are linked to the formation of multiple mtDNA deletions (Kaukonen et al. ...
Research suggests that mitochondrial changes are a driving force, rather than a consequence, of the aging process and Alzheimers disease pathogenesis. Although point mutations of mitochondrial DNA have been hypothesized as being a critical cause of aging, there is evidence that they may not be fully explanatory. Mitochondria are dynamic organelles with very short half-lives. Continuous replication of mitochondrial DNA (mtDNA) is required for assignment to new mitochondria, resulting in a significant error rate and accumulation of mutated in mtDNA genome over time and space. We hypothesized that, beyond point mutations, different types of mtDNA rearrangements should be extensively distributed in aging cells. As these rearrangements are often not detected by routine methods such as polymerase chain reaction, we applied the approach of directly sequencing mtDNA from isolated mitochondria derived from fresh frozen brain samples. Our data show that different types of mitochondrial rearrangements are ...
Mutations in mitochondrial DNA (mtDNA) may cause maternally-inherited cardiomyopathy and heart failure. In homoplasmy all mtDNA copies contain the mutation. In heteroplasmy there is a mixture of normal and mutant copies of mtDNA. The clinical phenotype of an affected individual depends on the type of genetic defect...
Mitochondrial-nucleus cross-talks and mitochondrial retrograde regulation of nuclear genes can play significant role in cellular properties. Several studies reported that somatic mitochondrial DNA alterations are often detected in cancer cells. Most of such alterations are polymorphisms without functional significance. Here we use a transmitochondrial cybrid (cybrids) approach to understand the significance of mitochondrial property in regulating the oncogenic properties of a cell irrespective of its mutational and nuclear status. Cybrid models in two differently defined nuclear backgrounds were studied. In the first model, mitochondria depleted rho zero (≥0) from an aggressive osteosarcoma cell lines 143B TK− was used as a common nuclear background. 143B β0 cells were fused with mitochondria from non-cancerous breast epithelial cell line MCF10A, low metastatic breast cancer cell line MDA-MB-468 and highly metastatic 143B TK− cell lines. In the second model, we used the common nuclear ...
Title:Direct Quantification of Mitochondria and Mitochondrial DNA Dynamics. VOLUME: 13 ISSUE: 14. Author(s):Yasutomo Nomura. Affiliation:Department of Systems Life Engineering, Maebashi Institute of Technology, 460-1 Kamisadori, Maebashi, Japan.. Keywords:Mitochondria, mtDNA, image correlation spectroscopy, fusion, fission, cytoskeleton, fluorescence microscopy, major organelles, cell, cytoskeletal tracks , mitochondrial DNA dynamics, metabolic diseases, compounds, heterogeneous environment. Abstract:Mitochondria are known to be one of major organelles within a cell and to play a crucial role in many cellular functions. These organelles show the dynamic behaviors such as fusion, fission and the movement along cytoskeletal tracks. Besides mitochondria, mitochondrial DNA is also highly motile. Molecular analysis revealed that several proteins are involved in mitochondria and mitochondrial DNA dynamics. In addition to the degeneration of specific nerves with high energy requirement, mutation of ...
In wild-type Saccharomyces cerevisiae, erythromycin and certain other antibacterial antibiotics inhibit the formation of respiratory enzymes in mitochondria by inhibiting translation on mitochondrial ribosomes. This paper is concerned with the origin of mutant cells, resistant to erythromycin by virtue of having a homogeneous population of mutant mitochondrial DNA molecules. Such mutant cells are obtained by plating wild-type (sensitive) cells on a nonfermentable substrate plus the antibiotic. Colonies of mutant cells appear first about four days after the time of appearance of established mutant cells; new colonies continue to appear, often at a constant rate, for many days. Application of the Newcombe respreading experiment demonstrates that most or all of the mutant cells which form the resistant colonies on selective medium arise only after exposure of the population to erythromycin. It is suggested that this result is most probably due to intracellular selection for mitochondrial genomes. Resistant
Mitochondrial DNA (mtDNA) encodes for proteins required for oxidative phosphorylation, and mutations affecting the genome have been linked to a number of diseases as well as the natural ageing process in mammals. Human mtDNA is replicated by a molecular machinery that is distinct from the nuclear replisome, but there is still no consensus on the exact mode of mtDNA replication. We here demonstrate that the mitochondrial single-stranded DNA binding protein (mtSSB) directs origin specific initiation of mtDNA replication. MtSSB covers the parental heavy strand, which is displaced during mtDNA replication. MtSSB blocks primer synthesis on the displaced strand and restricts initiation of light-strand mtDNA synthesis to the specific origin of light-strand DNA synthesis (OriL). The in vivo occupancy profile of mtSSB displays a distinct pattern, with the highest levels of mtSSB close to the mitochondrial control region and with a gradual decline towards OriL. The pattern correlates with the replication ...
DeSalle, R. and Giddings, L.V. (1986) Discordance of Nuclear and Mitochondrial DNA Phylogenies in Hawaiian Drosophila. Proceedings of the National Academy of Sciences, 83, 6902-6906.
Researchers from Salk Institute in San Diego, CA have presented a breakthrough study on the elimination of defective mitochondrial DNA (mtDNA). The use of genome editing tools -restriction endonucleases and transcription activator-like effector nucleases (TALENs)- allowed them to succesfully target specific mtDNA mutations and reduce their transgenerational tranmission. The tests have been carried out on mice oocytes and one cell embryos. The findings could be applied in the future to treat human mitochondrial diseases.. Mitochondria are fundamental for the cell, being energy production their main duty. Defects in these organelles are especially dramatic for high energy-consuming organs like the heart and the brain. There is no cure for mitochondrial diseases, but their transmission can be reduced by pre-impantation genetic diagnosis; however, the risk in far from zero, and embryo manipulation can affect its viability. A recently developed alternative is to transfer the genome into a donor ...
Full Text - Human TP53 gene is characterised by a polymorphism at codon 72 leading to an Arginine-to-Proline (R/P) substitution. The two resulting p53 isoforms have a different subcellular localisation after stress (more nuclear or more mitochondrial for the P or R isoform, respectively). p53P72 variant is more efficient than p53R72 in inducing the expression of genes involved in nuclear DNA repair. Since p53 is involved also in mitochondrial DNA (mtDNA) maintenance, we wondered whether these p53 isoforms are associated with different accumulation of mtDNA damage. We observed that cells bearing p53R72 accumulate lower amount of mtDNA damage upon rotenone stress with respect to cells bearing p53P72, and that p53R72 co-localises with polymerase gamma more than p53P72. We also analysed the in vivo accumulation of heteroplasmy in a 300 bp fragment of mtDNA D-loop of 425 aged subjects. We observed that subjects with heteroplasmy higher than 5% are significantly less than expected in the p53R72/R72 group. On
An article seeking answers to the question, why is mitochondrial DNA important? Mitochondrial DNA contributes to energy production and protein assembly. Mitochondrial DNA is also being increasingly used by forensic scientists to track down criminals.
We show that elevated mtDNA copy number in peripheral blood is associated with autism, indicating that there may be mitochondrial dysfunction in children with autism.
The spectrum of mitochondrial DNA (mtDNA) variation in India clearly supports the African origin of modern humans. In their deepest branching points Indian mtDNA clusters share common combinations of...