Mitochondrial mutations. Medical search. Frequent questions

Unlike any other part of the cell, mitochondria have their own mitochondrial DNA (mtDNA), which encodes 13 of the thousands of protein subunits of the ETS. (sens.org)
Mitochondria with deletion mutations thus have a selective advantage over healthy or mildly damaged mitochondria, with the result that once even one mitochondrion suffers a deletion, its progeny quickly take over the entire cell. (sens.org)
We therefore sequenced a small portion of the hypervariable D-loop region of mitochondria from individuals with HCC in matching tumour and nontumour liver tissue to determine the frequency of mitochondrial mutations. (nature.com)
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, such as adenosine triphosphate (ATP). (wikipedia.org)
Detailed functional analysis of mitochondria harbouring this novel mutation demonstrates a fragmented mitochondrial network with a decreased mitochondrial mass in patient fibroblasts. (uni-muenchen.de)
To show the pathogenicity of these mutations, we characterized the structure, adenosine triphosphate (ATP) content, bioelectric characteristics and functions of mitochondria in cultured primary fibroblasts obtained from the proband and her parents. (fortuneonline.org)
The alteration of the mitochondrial network only when cells are challenged in aerobiosis testifies to the fragility of mitochondria, which are unable to meet the metabolic needs of neurons. (fortuneonline.org)
In this study, we introduced a light-driven proton transporter, Delta-rhodopsin (dR), to Drosophila mitochondria, where the mitochondrial proton-motive force (Δp) and mitochondrial membrane potential are maintained in a light-dependent manner. (nature.com)
Light-dependent activation of mitochondrion-targeted dR (mito-dR) but not a mito-dR inactive mutant successfully transformed mitochondria from an OXPHOS-dependent powerhouse to a photoenergetic powerhouse, which accordingly reinforced the mitochondrial functions of the nerve terminals in terms of ATP production and Ca 2+ -buffering activity, suppressing ROS generation 10 , 11 . (nature.com)
Recent studies associated certain type of cardiovascular disease (CVD) with specific mitochondrial DNA (mtDNA) defects, mainly driven by the central role of mitochondria in cellular metabolism. (uab.cat)
Moreover, the mitochondria in these cells display lowered motility, and the number of axonal mitochondria in neurons expressing disease-causing mutations in ATL3 is strongly decreased. (uantwerpen.be)
When MitoTracker Deep Red-labeled high-metastatic Lewis lung carcinoma A11 cells carrying the ND6 G13997A mtDNA mutation were cocultured with CellLight mitochondria-GFP-labeled low-metastatic P29 cells harboring wild-type mtDNA, bidirectional transfer of red- and green-colored vesicles, probably mitochondria-related EVs, was observed in a time-dependent manner. (biomedcentral.com)
The hmtRNAMet serves both in translational initiation and elongation in human mitochondria making this tRNA of particular interest in mitochondrial protein synthesis. (ncsu.edu)
In particular, a number of the long range interactions between the D- and T-arms of the tRNAs appear to be missing.All 22 tRNAs that function in mammalian mitochondria are encoded in the mitochondrial DNA. (ncsu.edu)
This mutation presents as splenic lymphoma, is largely confined to lymphocyte cells, and results in severely abnormal mitochondria leading to serious defects in energy production (22Lombes A. Bories D. Girodon E. Franchon P. Ngo M. Breton-Gorious J. Tulliez M. Goossens M. Hum. (ncsu.edu)
The 8U→C mutation leads to a myopathy presumably arising from a reduction in translational activity in mitochondria. (ncsu.edu)

The disease-causing mutations disclosed in mitochondrial carriers range from point mutations, which are often localized in the substrate translocation pore of the carrier, to large deletions and insertions. (nih.gov)
More than 200 point mutations in mitochondrial DNA (mtDNA) have been reported in the mtDNA mutation database MITOMAP. (biomedcentral.com)
Point mutations of muscle mitochondrial DNA from patients with mitochondrial encephalomyopathies. (cdc.gov)

Later, numerous disorders caused by mutations in the nuclear genes encoding mitochondrial proteins were found. (nih.gov)
A group of these diseases are due to defects of mitochondrial carriers, a family of proteins named solute carrier family 25 (SLC25), that transport a variety of solutes such as the reagents of ATP synthase (ATP, ADP, and phosphate), tricarboxylic acid cycle intermediates, cofactors, amino acids, and carnitine esters of fatty acids. (nih.gov)
And because the stretch of mtDNA which is most prone to deletion mutations during aging encodes machinery that is essential to protein synthesis from any mitochondrial genes, the most common deletion seen in the mtDNA of aging cells can render a mitochondrion unable to make a single one of the 13 mitochondrially-encoded proteins that are critical components of their energy-generating system. (sens.org)
With a few exceptions, animals have 37 genes in their mitochondrial DNA: 13 for proteins, 22 for tRNAs, and 2 for rRNAs. (wikipedia.org)
found that the majority of mtDNA somatic mutations in medulloblastomas existed in regions of mononucleotide repeats, rather than in genes encoding proteins for the respiratory chain complexes [ 35 ]. (biomedcentral.com)
It has been hypothesized that a point mutation of PMP22 makes the protein dysfunctional while duplication may compromise stoichiometry and interactions with other myelin proteins [6]. (fortuneonline.org)
MRPP2 also moonlights in a complex with the MRPP1 (also known as TRMT10C) protein for N1-methylation of purines at position 9 of mitochondrial tRNA, and in a complex with MRPP1 and MRPP3 (also known as PRORP) proteins for 5'-end processing of mitochondrial precursor tRNA. (ox.ac.uk)
The mitochondrial genome encodes 13 proteins necessary for energy production, two rRNAs and all of the 22 tRNAs required for the synthesis of these proteins (1Attardi G. Int. Rev. Cytol. (ncsu.edu)
Mitochondrial dysfunction and loss of Parkinson's disease-linked proteins contribute to neurotoxicity of manganese -containing welding fumes. (cdc.gov)
A similar regimen of manganese chloride (MnCl2) also caused extensive loss of striatal TH, mitochondrial electron transport components, and Park proteins. (cdc.gov)
90% of mitochondrial proteins are coded by nuclear genes. (msdmanuals.com)

We describe a novel mtDNA mutation in a patient who developed chronic kidney disease. (elsevierpure.com)
We outline mechanisms that may underlie the occurrence of chronic kidney disease in the setting of this novel mtDNA mutation. (elsevierpure.com)
A total of 18 of 20 patients had at least one somatic mtDNA mutation in their tumour samples. (upm.edu.my)
The mitochondrial 12S rRNA A1555G mutation is the most prevalent deafness-causing mitochondrial DNA (mtDNA) mutation and is inherited maternally. (biomedcentral.com)
Her mother also suffered from diabetes mellitus with deafness and her son, who was not diabetic at age 19, had the same mitochondrial DNA (mtDNA) mutation. (elsevierpure.com)
At 44 years of age, she developed congestive heart failure due to cardiomyopathy, and the same mtDNA mutation was identified in the cardiac muscle. (elsevierpure.com)

Background Mitochondrial DNA (mtDNA) diseases are rare disorders whose prevalence is estimated around 1 in 5000. (bmj.com)

The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) has strokelike events that are acute in onset, often transient, and occasionally associated with a febrile illness. (medscape.com)
The prevalence of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) is 16-18/100,000, with the highest reported diagnostic rate in Western regions and the lowest rate in Asia. (medscape.com)
It is used to cut a mutation that causes mitochondrial encephalomyopathy and stroke-like episodes syndrome in patient-derived induced pluripotent stem cells. (edu.sa)
Mitochondrial mutations have been fully described in the literature with regard to their presentation in patients with pediatric epilepsy, but the genetics are poorly described in adult populations, with the two most common epileptic pathologies being mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes and myoclonic epilepsy with ragged red fibers [ 3 ]. (e-jnc.org)
Thymidine phosphorylase gene mutations in patients with mitochondrial neurogastrointestinal encephalomyopathy syndrome. (cdc.gov)

Here, we report the results of a comprehensive study on OPA3 mutations, including the mutation spectrum and its prevalence in a large cohort of OPA1-negative autosomal dominant optic atrophy (ADOA) patients, the associated clinical phenotype and the functional characterisation of a newly identified OPA3 mutant. (uni-muenchen.de)
We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l) gene, which has been shown to be critical for mitochondrial fission. (ljmu.ac.uk)
2)Five unrelated patients harboring the A3243G mutation in the mitochondrial DNA (mtDNA) but presenting with different clinical phenotype were studied for their percentage of mutation at the single muscle fiber levels. (nii.ac.jp)
Phenotype heterogeneity associated with mitochondrial DNA A3243G mutation]. (cdc.gov)

We speculate that PMP22 may promote mitochondrial dysfunction, myelin having a role in mitochondrial metabolism. (fortuneonline.org)
These findings suggest that specific MFN2 mutations cause tissue-selective mitochondrial dysfunction with increased adipocyte proliferation and survival, confirm a novel form of excess adiposity with paradoxical suppression of leptin expression, and suggest potential targeted therapies. (univpm.it)
The underlying mechanism of PRIS is unknown, but some studies suggest that underlying mitochondrial dysfunction may predispose patients to developing PRIS. (e-jnc.org)
Drosophila CHCHD2 ( dCHCHD2 ) knockout flies exhibit PD-like phenotypes in an age-dependent manner, which include dysfunction in motor ability, DA neuron loss, increased oxidative stress and mitochondrial cristae degeneration 2 . (nature.com)
Its role in the regulation of normal mitochondrial function and in different disease states attributed to mitochondrial dysfunction is not known. (nih.gov)
As mutations in PARK genes have been linked to early-onset PD in humans, and because welding is implicated as a risk factor for parkinsonism, PARK genes might play a critical role in WF-mediated dopaminergic dysfunction. (cdc.gov)
Jake was also later diagnosed with mitochondrial dysfunction, adding to the severity and complexity of his disease. (medlineplus.gov)

While genomic DNA is complex, the human mitochondrial genome is only 16.5 kb in length, encoding 13 polypeptides of the respiratory chain, 22 transfer RNAs and two rRNAs ( Taanman, 1999 ). (nature.com)
Human mitochondrial DNA was the first significant part of the human genome to be sequenced. (wikipedia.org)
Structures of the human mitochondrial ribosome bound to EF-G1 reveal distinct features of mitochondrial translation elongation. (nih.gov)
Lee, YS, Kennedy, WD & Yin, YW 2009, ' Structural Insight into Processive Human Mitochondrial DNA Synthesis and Disease-Related Polymerase Mutations (DOI:10.1016/j.cell.2009.07.050) ', Cell , vol. 139, no. 4, pp. 828. (utmb.edu)
A Disease-causing Point Mutation in Human Mitochondrial tRNA(Met) Results in tRNA Misfolding Leading to Defects in Translational Initiation and Elongation. (ncsu.edu)
A single point mutation (T4409C) in the gene for human mitochondrial tRNAMet (hmtRNAMet) has been found to cause mitochondrial myopathy. (ncsu.edu)
Human mitochondrial tRNAMet transcripts for aminoacylation experiments were prepared by in vitro transcription using the hammerhead ribozyme construct described previously (23Spencer A.C. Heck A.H. Takeuchi N. Watanabe K. Spremulli L.L. Biochemistry. (ncsu.edu)
The protein sample was dialyzed against 2 volumes of 500 ml of dialysis buffer (50 mm Tris-HCl, pH 7.6, 50 mm KCl, 2.5 mm MgCl2, 0.1 mm EDTA, 10% glycerol and 7 mm ;ME) for 1 h.Cells carrying a plasmid encoding the His6-tagged human mitochondrial MetRS were grown as described (23Spencer A.C. Heck A.H. Takeuchi N. Watanabe K. Spremulli L.L. Biochemistry. (ncsu.edu)
Reaction mixtures (100 ;l) contained 50 mm Tris-HCl, pH 7.6, 2.5 mm MgCl2, 2.5 mm ATP, 0.2 mm spermine, 200 ;g/ml bovine serum albumin, 0.2 units/;l SUPERase·In RNase inhibitor, 40 ;m [35S]methionine (4,000 cpm/pmol), 50 nm human mitochondrial MetRS or 8 nm E. coli MetRS, and 1 ;m U8 or 8U→C hmtRNAMet. (ncsu.edu)
Reaction mixtures (2 ml) were prepared as described above except that 20 ;m [35S]methionine (20,000 cpm/pmol), 0.5 ;m U8, or 8U→C hmtRNAMet, and saturating amounts of human mitochondrial MetRS were used. (ncsu.edu)
To determine the biochemical consequence of the 8U→C mutation, the abilities of the U8 and 8U→C hmtRNAMet transcripts to be aminoacylated by the human mitochondrial methionyl-tRNA synthetase (hmMetRS) were tested. (ncsu.edu)

The biochemical consequences of deficient transport are the compartmentalized accumulation of the substrates and dysfunctional mitochondrial and cellular metabolism, which frequently develop into various forms of myopathy, encephalopathy, or neuropathy. (nih.gov)
Mitochondrial myopathy associated with a novel mutation in mtDNA. (bvsalud.org)
One patient had a clinically and pathologically defined Leigh syndrome (LS), two showed mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS), another showed progressive external ophthalmoplegia (PEO), and the other showed mitochondrial diabetes mellitus (MDM). (nii.ac.jp)
The mitochondrial DNA C3303T point mutation can cause cardionyopathy, myopathy,(or Goth). (nii.ac.jp)
This mutation leads to mitochondrial myopathy resulting in dystrophic muscles and exercise intolerance (20Vissing J. Salamon M.B. Arlien-Soborg P. Norby S. Manta P. DiMauro S. Schmalbruch H. Neurology. (ncsu.edu)

The frequency of mutation and deletion of specific areas of the mitochondrial genome in tumour and matched normal tissue of patients with HBV infection was investigated in the current study. (nature.com)
Although various deletions of the mitochondrial genome have been reported, the 4977 bp deletion is the most widespread and has been associated with ageing in tissues ( Kowald, 1999 ). (nature.com)
Pioneering single-cell sequencing technology sheds light on risk of mitochondrial genome editing and hidden mitochondrial mutations in human oocytes and synthetic embryos. (edu.sa)
A high-throughput single-cell single-mitochondrial genome sequencing technology known as iMiGseq has provided new insights into mutations of mitochondrial DNA (mtDNA) and offers a platform for assessing mtDNA editing strategies and genetic diagnosis of embryos prior to their implantation. (edu.sa)
In another experiment using the new technology, iMiGseq revealed the potential risks of unexpected large increases in the frequency of off-target mutations, known as heteroplasmy, in a mitochondrial genome editing method called mitoTALEN - a genome editing tool that cuts a specific sequence in mitochondrial DNA. (edu.sa)
The existence in some species of mitochondrion-derived organelles lacking a genome suggests that complete gene loss is possible, and transferring mitochondrial genes to the nucleus has several advantages. (wikipedia.org)
Across all organisms, there are six main mitochondrial genome types, classified by structure (i.e. circular versus linear), size, presence of introns or plasmid like structures, and whether the genetic material is a singular molecule or collection of homogeneous or heterogeneous molecules. (wikipedia.org)
Most (bilaterian) animals have a circular mitochondrial genome. (wikipedia.org)
The anemone Isarachnanthus nocturnus has the largest mitochondrial genome of any animal at 80,923 bp. (wikipedia.org)
The smallest known mitochondrial genome in animals belongs to the comb jelly Vallicula multiformis, which consist of 9,961 bp. (wikipedia.org)
In February 2020, a jellyfish-related parasite - Henneguya salminicola - was discovered that lacks a mitochondrial genome but retains structures deemed mitochondrion-related organelles. (wikipedia.org)
There are three different mitochondrial genome types in plants and fungi. (wikipedia.org)
Somatic mutations in the mitochondrial genome occur in numerous tumor types including brain tumors. (biomedcentral.com)
Two hypervariable regions of mononucleotide repeats occur in the mouse mitochondrial genome, i.e., the origin of replication of the light strand (O L ) and the Arg tRNA. (biomedcentral.com)
In this study we examined the entire mitochondrial genome in a series of chemically induced brain tumors in the C57BL/6J strain and spontaneous brain tumors in the VM mouse strain. (biomedcentral.com)
Mitochondrial DNA (mtDNA) is essential for the production of subunits for the electron transport chain, since it encodes peptides for Complex I, III, IV, and V. The mitochondrial genome consists of a 16.5 kb piece of circular DNA encoding 37 genes on the L and H strands. (biomedcentral.com)
This higher mutation rate may be due in part to a lack of protective histones, reduced fidelity of polymerase γ, or to the localization of the mitochondrial genome to the inner mitochondrial membrane near damaging reactive oxygen species [ 5 - 9 ]. (biomedcentral.com)
Other studies of the mitochondrial genome focused on mtDNA copy number in brain tumors [ 34 ]. (biomedcentral.com)
In the only study examining the entire mitochondrial genome, Wong et al . (biomedcentral.com)

To characterise a novel OPA3 mutation, we analysed the mitochondrial import, steady-state levels and the mitochondrial localisation of the mutated protein in patients' fibroblasts. (uni-muenchen.de)
There was strong transcriptional evidence of mitochondrial stress signalling, increased protein synthesis, and suppression of signatures of cell death in affected tissue, whereas mitochondrial morphology and gene expression were normal in skin fibroblasts. (univpm.it)
Clinical, neuroimaging and biochemical findings in patients and patient fibroblasts expressing ten novel GFM1 mutations. (nih.gov)

Mitochondrial Oxidative Phosphorylation Disorders Impairment of oxidative phosphorylation often, but not always, causes lactic acidosis, particularly affecting the central nervous system, retina, and muscle. (msdmanuals.com)

Heteroplasmic mutations, inherited from egg cells, can cause congenital diseases, like maternally inherited Leigh syndrome, and are associated with late-onset complex diseases. (edu.sa)
Next-generation sequencing has been used to sequence mtDNA and implicated heteroplasmic mutations as significant contributors to metabolic disease. (edu.sa)
Molecular epidemiology of childhood mitochondrial encephalomyopathies in a Finnish population: sequence analysis of entire mtDNA of 17 children reveals heteroplasmic mutations in tRNAArg, tRNAGlu, and tRNALeu(UUR) genes. (cdc.gov)

The iMiGseq method provides a novel means to accurately depict the complete haplotypes of individual mtDNA in single cells, offering an ideal platform for explaining the cause of mitochondrial mutation-related diseases, evaluating the safety of various mtDNA editing strategies and unraveling the links between mtDNA mutations, ageing and the development of complex diseases. (edu.sa)

Mitochondrial DNA heteroplasmy is modulated during oocyte development propagating mutation transmission. (cam.ac.uk)
MtDNA CR mutations (both fixed and in heteroplasmy) were analysed in two demographically-matched case-control samples, using 154 stroke cases, 211 MI cases and their corresponding control individuals. (uab.cat)
Based on detailed mtDNA analyses of the family members using next-generation sequencing with 1% sensitivity to mutated mtDNA, the level of heteroplasmy in terms of the A1555G mutation in blood DNA samples was quantified. (biomedcentral.com)
An individual harbored a heterogeneous A1555G mutation, at 28.68% heteroplasmy. (biomedcentral.com)
The individual's brother and mother did not carry the A1555G mutation, and both had less than 1% mitochondrial 12S rRNA A1555G heteroplasmy. (biomedcentral.com)

An epidemiologic study in northern Finland found the prevalence of the A3243G MELAS mutation (responsible for 80% of cases) to be 16.3 per 100,000. (medscape.com)
Clinical features of A3243G mitochondrial tRNA mutation. (cdc.gov)
Study on mitochondrial DNA gene tRNA(Leu(UUR)) A3243G mutation in type 2 diabetes mellitus]. (cdc.gov)
Mitochondrial DNA A3243G mutation involved in familial diabetes, chronic intestinal pseudo-obstruction and recurrent pancreatitis. (cdc.gov)
Protean phenotypic features of the A3243G mitochondrial DNA mutation. (cdc.gov)

Mitochondrial mutations in patients with congenital heart defects by next generation sequencing technology. (istanbul.edu.tr)
This study therefore identified two distinctive molecular mechanisms to explain the biochemical defects for the novel missense patient mutations. (ox.ac.uk)

In the 1980s, after the mitochondrial DNA (mtDNA) had been sequenced, several diseases resulting from mtDNA mutations emerged. (nih.gov)
Examples of diseases, due to mitochondrial carrier mutations are: combined D-2- and L-2-hydroxyglutaric aciduria, carnitine-acylcarnitine carrier deficiency, hyperornithinemia-hyperammonemia-homocitrillinuria (HHH) syndrome, early infantile epileptic encephalopathy type 3, Amish microcephaly, aspartate/glutamate isoform 1 deficiency, congenital sideroblastic anemia, Fontaine progeroid syndrome, and citrullinemia type II. (nih.gov)
Here, we review all the mitochondrial carrier-related diseases known until now, focusing on the connections between the molecular basis, altered metabolism, and phenotypes of these inherited disorders. (nih.gov)
as in all diseases with mitochondrial transmission, the disease is inherited via the ovum and hence always from the mother. (medscape.com)
This has revealed molecular features of rare mtDNA mutations that cause maternally inherited diseases. (edu.sa)
Mitochondrial diseases are a group of metabolic disorders. (medlineplus.gov)
Genetic mutations cause these diseases. (medlineplus.gov)
Thus, recent studies confirm that pathologic mitochondrial deoxyribo nucleic acid mutations are a major reason of diseases and determining them by next-generation sequencing will improve our understanding of dysregulation of heart development. (istanbul.edu.tr)
We also underscore the need to consider in relevant kidney diseases the presence of an underlying mitochondrial cytopathy because the latter more commonly exists than is generally recognized. (elsevierpure.com)
Considerable interest in mitochondrial tRNAs centers on the occurrence of diseases arising from mutations in their genes that lead to maternally inherited genetic disorders (9Wittenhagen L.M. Kelley S.O. Trends Biochem. (ncsu.edu)
The diseases associated with mitochondrial tRNA mutations may arise from failure in the processing of the tRNA (13Levinger L. Jacobs O. James M. Nucleic Acids Res. (ncsu.edu)

Several studies have described many mutations in mitochondrial genes encoding for subunits of respiratory chain complexes. (istanbul.edu.tr)
In this regard, substantial interest surrounds the occurrence of kidney disease in primary mitochondrial cytopathies, a heterogeneous group of conditions in which mutations in mitochondrial DNA (mtDNA) or nuclear DNA impair the functionality of components of the mitochondrial respiratory chain. (elsevierpure.com)
Mitochondrial translation is crucial for maintaining mitochondrial function and mutations in this system lead to a breakdown in the respiratory chain-oxidative phosphorylation system and to impaired maintenance of mitochondrial DNA. (nih.gov)

To analyse mitochondrial deoxyribo nucleic acid mutations, the entire mitochondrial deoxyribo nucleic acid was amplified in two overlapping polymerase chain reaction fragments from the cardiac tissue of the 22 patients with congenital heart disease, undergoing cardiac surgery. (istanbul.edu.tr)

We employ mitochondrial single-cell assay for transposase-accessible chromatin with sequencing to profile 163,279 cells from 9 patients with chronic lymphocytic leukemia (CLL) collected across disease course and utilize mitochondrial DNA (mtDNA) mutations as natural genetic markers of cancer clones. (nih.gov)
We observe stable propagation of mtDNA mutations over years in the absence of strong selective pressure, indicating clonal persistence, but dramatic changes following tight bottlenecks, including disease transformation and relapse posttherapy, paralleled by acquisition of copy-number variants and changes in chromatin accessibility and gene expression. (nih.gov)
mtDNA mutations thus mirror disease history and provide naturally occurring genetic barcodes to enable patient-specific study of cancer subclonal dynamics. (nih.gov)
Single-cell multi-omic profiling of CLL reveals the utility of somatic mtDNA mutations as in vivo barcodes, which mark subclones that can evolve over time along with changes in accessible chromatin and gene expression profiles to capture dynamics of disease evolution. (nih.gov)
Methods We analysed the whole mtDNA in a cohort of 743 patients suspected of manifesting a mitochondrial disease, after excluding deletions and common mutations. (bmj.com)
Heteroplasmic mitochondrial DNA (mtDNA) mutations are a common cause of inherited disease, but a few recurrent mutations account for the vast majority of new families. (cam.ac.uk)
This could explain how a disadvantageous mutation in a carrier increases to levels that cause disease but fails to fixate, causing multigenerational heteroplasmic mtDNA disorders. (cam.ac.uk)
other distant mtDNA genetic variants may be unintentionally affected by the editing of a genetically linked disease-relevant mutation and there is a need for ultrasensitive methods to assess the safety of editing strategies," says Li. (edu.sa)
The symptoms of mitochondrial disease can vary. (medlineplus.gov)
What Is Mitochondrial Disease? (medlineplus.gov)
This study represents the most comprehensive mitochondrial deoxyribo nucleic acid mutational analysis in patients with congenital heart disease. (istanbul.edu.tr)
In human kidney disease, mitochondrial ultrastructural damage has long been recognized. (elsevierpure.com)
Although the extent to which such mitochondrial changes contribute to human kidney disease is uncertain, experimental studies clearly demonstrate that mitochondrial damage can instigate pathogenetic processes that drive ongoing kidney disease. (elsevierpure.com)
Clinical credence for this experimentally based hypothesis is provided by the development of kidney disease in patients with primary mitochondrial disorders. (elsevierpure.com)
Charcot-Marie-Tooth disease type 2A (CMT2A) is an inherited axonal peripheral neuropathy mainly caused by mutations in the mitofusin 2 (MFN2) gene encoding for the MFN2 protein, a GTPase involved in the mitochondrial dynamics and bioenergetics. (fortuneonline.org)
Mitochondrial degeneration is considered one of the major causes of Parkinson's disease (PD). (nature.com)
These results confirm the concept that differences in the mutation load and in the spatial distribution of the mutation among different cells and tissues are responsible for the differences in phenotypical expression of the disease. (nii.ac.jp)
PARK2 (parkin) mutations cause early-onset Parkinson's disease (PD). (ox.ac.uk)
The mitochondrial tRNA genes are hot spots for mutations that lead to human disease. (ncsu.edu)
This work establishes a foundation for understanding the physiological consequences of the numerous mitochondrial tRNA mutations that result in disease in humans. (ncsu.edu)
Cardiomyopathy due to mitochondrial disease may produce typical cardioembolic strokes in some patients. (medscape.com)
Some mitochondrial mutations may give rise to "overlap" syndromes, which present with clinical features of more than one disease entity. (medscape.com)
Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease. (cdc.gov)
[ 1 ] However, in children, this condition most often has an idiopathic or genetic origin, such as 22q11.2 microdeletion syndrome, autoimmune polyglandular syn-drome type 1 (APS1), hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome, hypoparathyroidism-retardation-dysmorphism (HRD) syndrome or mitochondrial disease. (medscape.com)
Mutations in the HTRA2 gene are associated with Type 13 PARKINSON DISEASE. (bvsalud.org)

This has revealed complex patterns of pathogenic mtDNA mutations, including single nucleotide variants and large structural variants. (edu.sa)
Mitochondrial DNA (mtDNA) carrying certain pathogenic mutations or single nucleotide variants (SNVs) enhances the invasion and metastasis of tumor cells, and some of these mutations are homoplasmic in tumor cells and even in tumor tissues. (biomedcentral.com)
We and others previously showed that certain mitochondrial DNA (mtDNA) somatic mutations or single nucleotide variants (SNVs) enhanced the invasion and metastasis of mouse and human cell lines, e.g. (biomedcentral.com)
For quantitative analysis of the mutation frequency at nucleotide 1555 in the control group and members of Family 2362, capture and next-generation sequencing (NGS) of a 147-bp DNA fragment corresponding to positions 1466-1612 of the mitochondrial 12S rRNA gene was performed on the Ion Proton System. (biomedcentral.com)
No data are currently available that examine the structure of mammalian mitochondrial tRNAs with single nucleotide resolution. (ncsu.edu)

However, the prevalence of rare mtDNA mutations is not known. (bmj.com)

Investigation of the relationship between somatic mtDNA mutations and protein expression levels of MnSOD2, CC3, LC3B, Beclin-1, BNIP3 and Parkin showed no significant differences. (upm.edu.my)

We hypothesised that increased oxidative stress associated with HBV infection in individuals with HCC would lead to an increased burden of mitochondrial DNA mutation. (nature.com)
Under oxidative stress conditions, ATP production was reduced and the proband cells showed a decrease of the mitochondrial fusion with small connected networks and a decrease of the mitochondrial volume. (fortuneonline.org)
Mitochondrial DNA (mtDNA) mutations, oxidative stress and resistance to cell deaths increase one's risk for breast cancer. (upm.edu.my)
This study aims to identify the types of mtDNA mutations, levels of protein expression of oxidative stress, apoptosis, autophagy and mitophagy in breast cancer as well as the association between mtDNA mutations and the levels of protein expression. (upm.edu.my)

The percentage of control subjects harbouring D-loop mutations was 11%, which was significantly lower than that observed in both the noncancerous (49%, P =0.033) and tumour tissue (59%, P =0.014) of patients with HCC. (nature.com)
Patients are usually tested only for deletions and for common mutations of mtDNA which account for 5-40% of cases, depending on the study. (bmj.com)
Patients carrying deleterious mutations showed symptoms before 16 years of age in 67% of cases. (bmj.com)
Mitochondrial mutations in patients with. (istanbul.edu.tr)
A total of 13 novel mitochondrial deoxyribo nucleic acid mutations were identified in nine patients. (istanbul.edu.tr)
Of the patients, three have novel mutations together with reported cardiomyopathy mutations. (istanbul.edu.tr)
Mutations in OPA3 have been reported in patients with autosomal dominant optic atrophy plus cataract and Costeff syndrome. (uni-muenchen.de)
Mutation analysis was carried out in a patient cohort of 121 independent ADOA patients. (uni-muenchen.de)
We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. (univpm.it)
We discuss the treatment strategy utilized in hopes of raising awareness of the risks in managing patients with epilepsy who have a potential underlying mitochondrial disorder. (e-jnc.org)
j50] Toure S, Mbaye F, Gueye MD, Fall M, Dem A, Lamy JB , Sembene M. Somatic mitochondrial mutations in oral cavity cancers among senegalese patients . (lesfleursdunormal.fr)
Furthermore, the frequency of predicted pathogenic mtDNA mutations was significantly correlated with distant metastasis in patients with non-small cell lung carcinoma (NSCLC) and colon cancers [ 2 ]. (biomedcentral.com)
1)In order to know the steady-state levels of RNA 19 in normal human tissues and the actual levels of it in MELAS patients, we analyzed the total RNA from various human tissues from 8 normal individuals, and biopsied muscles from 4 MELAS patients having MELAS-3243 point mutation. (nii.ac.jp)
The mutation load was greater in the muscle from the patient with LS (92%), who showed more than 80% even in the non-ragged red fibers (RRF) and also presented the highest proportion of RRF.The patients with MELAS had lower mutation levels as well as lower proportion of RRF, and these two parameters were even lower in the PEO and MDM patients. (nii.ac.jp)
As controls, 200 individuals negative for GJB2 , SLC26A4 , and mtDNA 12S rRNA mutations were recruited, including 100 individuals with normal hearing (Group 1) and 100 patients with sensorineural hearing loss (Group 2). (biomedcentral.com)
No evidence of patients and even within the same gene is expected somatic mutations was found in this study. (cdc.gov)

However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. (ljmu.ac.uk)

The study was carried out to determine whether mitochondrial DNA abnormalities were associated with HCC in individuals with HBV. (nature.com)
The patient exhibited mitochondrial abnormalities in both muscle and kidney, chronic tubulointerstitial changes, and recurrent episodes of rhabdomyolysis. (elsevierpure.com)
High-energy tissues (eg, muscle, heart, brain) are particularly at risk of malfunction due to mitochondrial abnormalities. (msdmanuals.com)
Maternal inheritance patterns characterize abnormalities of mitochondrial DNA. (msdmanuals.com)

The 4977 base pair "common deletion" that accumulates in some aging cells encodes all of the mitochondrial tRNAs and the genes for seven subunits of the mitochondrial electron transport chain. (sens.org)
MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. (univpm.it)
CHCHD2 (mutations of which cause an autosomal dominant form of PD) encodes a mitochondrial intermembrane protein 1 . (nature.com)
This gene encodes one of the mitochondrial translation elongation factors. (nih.gov)

The small fraction of hmtRNAMet that can be aminoacylated is not formylated by the mitochondrial Met-tRNA transformylase preventing its function in initiation, and it is unable to form a stable ternary complex with elongation factor EF-Tu preventing any participation in chain elongation. (ncsu.edu)

Variability may be due in part to variable mixtures of inherited mutant and normal mitochondrial genomes within cells and tissues. (msdmanuals.com)

Structural insights into mammalian mitochondrial translation elongation catalyzed by mtEFG1. (nih.gov)
Mammalian mitochondrial tRNAs have several unusual features that distinguish them from canonical tRNAs. (ncsu.edu)
However, small amounts of the aminoacylated 8U→C mutated hmtRNAMet could be isolated, permitting a limited investigation of additional steps in translation.In the mammalian mitochondrial system, the Met-tRNAMet must be formylated by the mitochondrial transformylase (MTFmt) to be used in initiation (19Spencer A.C. Spremulli L.L. Nucleic Acids Res. (ncsu.edu)

High-energy electrons are stripped from nutrients and used to fuel the four Complexes of the mitochondrial electron transport chain (ETS), which use the electrons' energy to pump hydrogen ions across a membrane inside the organelle. (sens.org)

which may involve large mitochondrial deletions in the cells of the basal ganglia) and many types of muscle disorders. (msdmanuals.com)

16 years) were associated with mutations in tRNA genes. (bmj.com)

This accumulation of RNA 19 observed in MELAS-muscle seems to be specific for the tRNALeu(UUR) mutation and related to the pathogenetic mechanism of MELAS. (nii.ac.jp)
MELAS exhibits dominat negative effects on mitochondrial RNA processing' Annals of Neurology. (nii.ac.jp)

A 44-year-old woman with diabetes mellitus, cardiomyopathy, and a mitochondrial gene mutation, was reported. (elsevierpure.com)
Diabetes mellitus with mitochondrial gene mutations in Japan. (cdc.gov)

Analysis of GFM1 gene mutations in a family with combined oxidative phosphorylation deficiency 1]. (nih.gov)

We aimed to identify the prevalence of We observed fewer mutations indicative of chloroquine several resistance markers, including genes that confer resistance over time, which may reflect reduced chlo- roquine pressure in specimens from travelers to Africa. (cdc.gov)

Mitochondrial disorders are equally common among males and females. (msdmanuals.com)
Mitochondrial disorders have maternal inheritance patterns. (msdmanuals.com)

C mutations could act as possible beneficial genetic factors for MI (conditional logistic regression: p = 0.001, p = 0.009 and p = 0.016, respectively). (uab.cat)
These results demonstrate the possible role of mtDNA mutations in the CR on the pathogenesis of stroke and MI, and show the importance of including this regulatory region in genetic association studies. (uab.cat)
We reviewed the genetic characteristics of families possessing the A1555G mutation in the database of the Genetic Testing Center for Deafness (PLA General Hospital, Beijing, China) and found a family (Family 2362) that did not fully conform to the maternal genetic characteristics (Fig. 1 ). (biomedcentral.com)
Despite a lot of testing, doctors were unable to determine a cause for his seizures until Jake was nearly 10 years old, when a test revealed he had a genetic mutation associated with Dravet syndrome. (medlineplus.gov)

MTND5 and MTND6 genes were identified as 'hotspots' of mutations, with Leigh syndrome accounting for the large majority of associated phenotypes. (bmj.com)
A mutation is most frequent in Leigh syndrome combined with reduced complex I activity, optic atrophy and/or Wolff-Parkinson-White. (cdc.gov)

Multiple correspondence analyses followed by hierarchical ascendant cluster process were used to explore relationships between clinical spectrum, age at onset and localisation of mutations. (bmj.com)
Comparison of the clinical phenotypes suggests that OPA3 mutations can additionally evoke hearing loss and by that extend the clinical manifestation of OPA3-associated optic atrophy. (uni-muenchen.de)
In summary, our study provides new insights into the clinical spectrum and the pathogenesis of dominant optic atrophy caused by mutations in the OPA3 gene. (uni-muenchen.de)
We aimed to discuss the clinical presentations of PRIS, along with a review of the mitochondrial POLG mutation found in our patient, which has also been described in other case reports of refractory adult-onset epilepsy. (e-jnc.org)

To elucidate the molecular mechanisms further, we investigated the association of PD-linked (Park) genes and mitochondrial function in causing dopaminergic abnormality. (cdc.gov)

Overall, 65 somatic mutations were identified, with 30 novel mutations. (upm.edu.my)
A total of 753 germline mutations were identified and four of which were novel mutations. (upm.edu.my)

Besides the known p.Q105E mutation, we observed a novel insertion, c.10_11insCGCCCG/p.V3_G4insAP which is located in the mitochondrial presequence. (uni-muenchen.de)

We identified a novel mutation, that was inherited from her mother, in the MFN2 protein (Met234Ile) in a Charcot-Marie-Tooth patient. (fortuneonline.org)
These results support the hypothesis that the mutation in the MFN2 gene altering mitochondrial bioenergetics and fusion causes axonal sensory-motor neuropathy. (fortuneonline.org)
Axonal CMTs, known as CMT2A, are mostly associated with mutations in the Mitofusin 2 ( MFN2 ) gene. (fortuneonline.org)
MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. (univpm.it)

Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). (ljmu.ac.uk)

It has been shown that mitochondrial deoxyribo nucleic acid mutations may play an important role in the development of cardiomyopathy, and various types of cardiomyopathy can be attributed to disturbed mitochondrial oxidative energy metabolism. (istanbul.edu.tr)
Identification of bioactive metabolites in human iPSC-derived dopaminergic neurons with PARK2 mutation: Altered mitochondrial and energy metabolism. (ox.ac.uk)

The mutation was not detected in any accessible tissues from his mother or siblings . (bvsalud.org)

Nuclear and mitochondrial DNA are thought to have separate evolutionary origins, with the mtDNA derived from the circular genomes of bacteria engulfed by the ancestors of modern eukaryotic cells. (wikipedia.org)
Recent analysis of a wide range of mtDNA genomes suggests that both these features may dictate mitochondrial gene retention. (wikipedia.org)
Mitochondrial genomes for animals average about 16,000 base pairs in length. (wikipedia.org)
Some plant species have enormous mitochondrial genomes, with Silene conica mtDNA containing as many as 11,300,000 base pairs. (wikipedia.org)

Loss of dCHCHD2 and introduction of PD-associated human CHCHD2 mutations destabilize cytochrome c, which transports an electron from complex III to complex IV during oxidative phosphorylation (OXPHOS), leading to a reduction in ATP production and the generation of reactive oxygen species (ROS) owing to the electron leak 2 . (nature.com)

Since the deafness caused by A1555G mutation in the mitochondrial 12S rRNA gene was first reported by Prezant et al. (biomedcentral.com)

PARK2 KO neurons displayed increased tricarboxylic acid (TCA) cycle activity, perturbed mitochondrial ultrastructure, ATP depletion, and dysregulation of glycolysis and carnitine metabolism. (ox.ac.uk)

Anatomy5

Organisms7

Diseases8

Chemicals and Drugs42

Analytical, Diagnostic and Therapeutic Techniques and Equipment22

Phenomena and Processes84

Information Science3

Named Groups2

Health Care4

Mitochondria16

Point mutations3

Proteins11

MtDNA mutation6

Background Mitochondrial DNA1

Encephalomyopathy5

Phenotype4

Dysfunction7

Human mitochondrial11

Myopathy5

Genome19

Fibroblasts3

Lactic acidosis1

Heteroplasmic mutations3

Cause of mitochondr1

Heteroplasmy5

A3243G5

Defects2

Diseases11

Respiratory chain3

Entire mitochondrial1

Disease25

Nucleotide5

Rare mtDNA mutations1

Somatic mtDNA mutations1

Oxidative stress4

Patients16

Pathogenic mutations1

Abnormalities4

Encodes4

Elongation factor1

Normal mitochondrial1

Mammalian mitochondrial3

Membrane1

Deletions1

TRNA genes1

MELAS2

Diabetes mellitus2

Gene mutations1

Prevalence1

Disorders2

Genetic4

Syndrome2

Clinical4

Molecular1

Novel mutations2

Presequence1

MFN24

Genes have been linked1

Energy metabolism2

Tissues1

Genomes4

Electron1

Deafness1

Neurons1