Mitochondrial Diseases in Man and Mouse
SciencePublished 5 March 1999
Douglas C. Wallace
Citations3,045
SJR quartileQ1
SJR score10.42
SNIP6.62
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The essential role of mitochondrial oxidative phosphorylation in cellular energy production, the generation of reactive oxygen species, and the initiation of apoptosis has suggested a number of novel mechanisms for mitochondrial pathology.
Abstract
Over the past 10 years, mitochondrial defects have been implicated in a wide variety of degenerative diseases, aging, and cancer. Studies on patients with these diseases have revealed much about the complexities of mitochondrial genetics, which involves an interplay between mutations in the mitochondrial and nuclear genomes. However, the pathophysiology of mitochondrial diseases has remained perplexing. The essential role of mitochondrial oxidative phosphorylation in cellular energy production, the generation of reactive oxygen species, and the initiation of apoptosis has suggested a number of novel mechanisms for mitochondrial pathology. The importance and interrelationship of these functions are now being studied in mouse models of mitochondrial disease.
Keywords
Biochemistry, Genetics and Molecular Biology
ScienceMitochondria and Apoptosis
8,994 Citations1998Douglas R. Green, John C. Reed
A variety of key events in apoptosis focus on mitochondria, including the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro- and antiapoptotic Bcl-2 family proteins.
Proceedings of the National Academy of SciencesOxidants, antioxidants, and the degenerative diseases of aging.
5,974 Citations1993B N Ames, Mark K. Shigenaga +1 more
It is argued that this damage to DNA, protein, and lipid is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts.
CellInduction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c
5,167 Citations1996Xuesong Liu, Caryn Naekyung Kim +3 more
Cells undergoing apoptosis in vivo showed increased release of cy tochrome c to their cytosol, suggesting that mitochondria may function in apoptosis by releasing cytochrome c.
NatureMolecular characterization of mitochondrial apoptosis-inducing factor
4,050 Citations1999Santos A. Susín, Hans Kristian Lorenzo +14 more
The identification and cloning of an apoptosis-inducing factor, AIF, which is sufficient to induce apoptosis of isolated nuclei is reported, indicating that AIF is a mitochondrial effector of apoptotic cell death.
ScienceMitochondrial DNA Mutation Associated with Leber's Hereditary Optic Neuropathy
2,431 Citations1988Douglas C. Wallace, Gurparkash Singh +6 more
This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.
Biochimica et Biophysica Acta (BBA) - Reviews on BiomembranesThe mitochondrial permeability transition
2,402 Citations1995Mario Zoratti, Ildikò Szabó
NatureA mutation in the tRNALeu(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies
2,085 Citations1990Yu‐ichi Goto, Ikuya Nonaka +1 more
An A-to-G transition mutation at nucleotide pair 3,243 in the dihydrouridine loop of mitochondrial tRNALeu(UUR) that is specific to patients with MELAS is reported, which creates an Apal restriction site and could perform a simple molecular diagnostic test for the disease.
NatureDeletions of muscle mitochondrial DNA in patients with mitochondrial myopathies
1,845 Citations1988Ian Holt, A. E. Harding +1 more
Observations demonstrate that mtDNA heteroplasmy can occur in man and that human disease may be associated with defects of the mitochondrial genome.
Nature GeneticsDilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase
1,778 Citations1995Yibing Li, Ting‐Ting Huang +10 more
Cytochemical analysis revealed a severe reduction in succinate dehydrogenase and aconitase activities in the heart and, to a lesser extent, in other organs, which indicates that MnSOD is required for normal biological function of tissues by maintaining the integrity of mitochondrial enzymes susceptible to direct inactivation by superoxide.
NatureThe genome sequence of Rickettsia prowazekii and the origin of mitochondria
1,695 Citations1998Siv G. E. Andersson, Alireza Zomorodipour +8 more
The complete genome sequence of the obligate intracellular parasite Rickettsia prowazekii, the causative agent of epidemic typhus, is described, which contains 834 protein-coding genes and is more closely related to mitochondria than is any other microbe studied so far.
ScienceHuman Cells Lacking mtDNA: Repopulation with Exogenous Mitochondria by Complementation
1,611 Citations1989Michael P. King, Giuseppe Attardi
Transformants obtained with various mitochondrial donors exhibited a respiratory phenotype that was in most cases distinct from that of the rho 0 parent or the donor, indicating that the genotypes of the mitochondrial and nuclear genomes as well as their specific interactions play a role in the respiratory competence of a cell.
Nature GeneticsMitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice
1,608 Citations1998Nils‐Göran Larsson, Jianming Wang +6 more
The mouse gene for mitochondrial transcription factor A (Tfam), formerly known as m-mtTFA, is disrupted by gene targetting of loxP-sites followed by cre-mediated excision in vivo and is the first mammalian protein demonstrated to regulate mtDNA copy number in vivo.
ScienceBax and Adenine Nucleotide Translocator Cooperate in the Mitochondrial Control of Apoptosis
1,170 Citations1998Isabel Marzo, Catherine Brenner +9 more
The proapoptotic molecule Bax and the constitutive mitochondrial protein ANT cooperate within the PTPC to increase mitochondrial membrane permeability and to trigger cell death.
Annals of NeurologyOxidative damage to mitochondrial DNA is increased in Alzheimer's disease
1,033 Citations1994Patrizia Mecocci, Usha MacGarvey +1 more
Results confirm that mitochondrial DNA is particularly sensitive to oxidative damage, and they show that there is increased oxidative damage to DNA in AD, which may contribute to the neurodegenerative process.
Proceedings of the National Academy of SciencesNeurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice.
1,021 Citations1996Russell M. Lebovitz, Henggui Zhang +6 more
Observations indicate that SOD2 deficiency causes increased susceptibility to oxidative mitochondrial injury in central nervous system neurons, cardiac myocytes, and other metabolically active tissues after postnatal exposure to ambient oxygen concentrations.
PubMedA new mitochondrial disease associated with mitochondrial DNA heteroplasmy.
1,006 Citations1990Ian Holt, A. E. Harding +2 more
Journal of Clinical InvestigationA CASE OF SEVERE HYPERMETABOLISM OF NONTHYROID ORIGIN WITH A DEFECT IN THE MAINTENANCE OF MITOCHONDRIAL RESPIRATORY CONTROL: A CORRELATED CLINICAL, BIOCHEMICAL, AND MORPHOLOGICAL STUDY
982 Citations1962Rolf Luft, Denis Ikkos +3 more
It was found that in the present patient this ability of the isolated skeletal muscle mitochondria was severely damaged.
ScienceThymidine Phosphorylase Gene Mutations in MNGIE, a Human Mitochondrial Disorder
900 Citations1999Ichizo Nishino, Antonella Spinazzola +1 more
Examination of 12 MNGIE probands revealed homozygous or compound-heterozygous mutations in the gene specifying thymidine phosphorylase (TP), indicating that loss-of-function mutations in TP cause the disease.
Nature GeneticsMitochondrial DNA deletions in human brain: regional variability and increase with advanced age
886 Citations1992Marisol Corral‐Debrinski, Terzah M. Horton +4 more
Changes in the accumulation of the common 4977 nucleotide pair (np) deletion in the cortex, putamen and cerebellum suggest that somatic mtDNA deletions might contribute to the neurological impairment often associated with ageing.
Nature GeneticsSomatic mutations of the mitochondrial genome in human colorectal tumours
838 Citations1998Kornélia Polyák, Yunbo Li +7 more
It is shown that mitochondria can rapidly become homogeneous in colorectal cancer cells using cell fusions and provide the first examples of homoplasmic mutations in the mtDNA of tumour cells, which have potential implications for the abnormal metabolic and apoptotic processes in cancer.
CellSpastic Paraplegia and OXPHOS Impairment Caused by Mutations in Paraplegin, a Nuclear-Encoded Mitochondrial Metalloprotease
829 Citations1998Giorgio Casari, Maurizio De Fusco +11 more
Analysis of muscle biopsies from two patients carrying Paraplegin mutations showed typical signs of mitochondrial OXPHOS defects, thus suggesting a mechanism for neurodegeneration in HSP-type disorders.
Annals of NeurologyOxidative damage to mitochondrial DNA shows marked age‐dependent increases in human brain
757 Citations1993Patrizia Mecocci, Usha MacGarvey +5 more
Results show for the first time that there is a progressive age‐related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected and it is possible that such damage may contribute to age‐dependent increases in incidence of neurodegenerative diseases.
Methods in enzymology on CD-ROM/Methods in enzymology[42]Assessment of mitochondrial oxidative phosphorylation in patient muscle biopsies, lymphoblasts, and transmitochondrial cell lines
743 Citations1996Ian A. Trounce, Yoon L. Kim +2 more
The approach to OX-PHOS investigation combines the identification of patients with OX -PHOS defects using more sensitive muscle biopsy studies followed by further biochemical characterization of primary defects in Epstein–Barr virus-transformed lymphoblasts.
The LancetDECLINE IN SKELETAL MUSCLE MITOCHONDRIAL RESPIRATORY CHAIN FUNCTION: POSSIBLE FACTOR IN AGEING
728 Citations1989Ian A. Trounce, Edward Byrne +1 more
A substantial fall in mitochondrial oxidative capacity in ageing muscle is suggested, which may contribute to reduced exercise capacity in elderly people and contribute to the ageing process in other organs.
Nature GeneticsMutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency
725 Citations1995Thomas Bourgeron, Pierre Rustin +6 more
A mutation in the nuclear–encoded flavoprotein (Fp) subunit gene of the succinate dehydrogenase (SDH) is reported in two siblings with complex II deficiency presenting as Leigh syndrome, the first report of a nuclear gene mutation causing a mitochondrial respiratory chain deficiency in humans.
Nature GeneticsSURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome
625 Citations1998Zhiqing Zhu, Jianbo Yao +11 more
Analysis of a candidate gene (SURF1) of unknown function revealed several mutations that suggest a role for SURF1 in the biogenesis of the COX complex and define a new class of gene defects causing human neurodegenerative disease.
Nature GeneticsMaternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion
616 Citations1992Scott W. Ballinger, John M. Shoffner +5 more
A pedigree with maternally transmitted DM and deafness for mitochondrial DNA mutations was tested and a 10.4 kilobase mtDNA deletion was discovered, demonstrating that DM can be caused by mtDNA mutations and suggests that some of the heterogeneity of this disease results from the novel features of mtDNA genetics.
Nature GeneticsRandom genetic drift in the female germline explains the rapid segregation of mammalian mitochondrial DNA
600 Citations1996Jack P. Jenuth, Alan C. Peterson +2 more
It is shown that the pattern of segregation can be explained by random genetic drift ocurring in early oogenesis, and that the effective number of segregating units for mtDNA is ∼200 in mice, which provides the basis for estimating recurrence risks for mitochondrial disease due to pathogenic mt DNA mutations and for predicting the rate of fixation of neutral mtDNA mutations in maternal lineages.
Proceedings of the National Academy of SciencesMitochondrial disease in superoxide dismutase 2 mutant mice
582 Citations1999Simon Melov, Pınar Coşkun +11 more
Results indicate that the increase in mitochondrial reactive oxygen species can result in biochemical aberrations with features reminiscent of mitochondrial myopathy, Friedreich ataxia, and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.
CellFamilial mitochondrial encephalomyopathy (MERRF): Genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease
575 Citations1988Douglas C. Wallace, Xianxian Zheng +6 more
The observed spectrum of clinical manifestations resulting from this heteroplasmic mtDNA mutation implies that mtDNA disease may be much more prevalent than previously anticipated.
Nature GeneticsA mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator
558 Citations1997Brett H. Graham, Katrina G. Waymire +4 more
‘knockout’ mice deficient in the heart/muscle isoform of the adenine nucleotide translocator (Ant1) have the biochemical, histological, metabolic and physiological characteristics of mitochondrial myopathy and cardiomyopathy.
The American Journal of Human GeneticsMutations of SURF-1 in Leigh Disease Associated with Cytochrome c Oxidase Deficiency
529 Citations1998Valeria Tiranti, Konstanze Hoertnagel +16 more
Sequence analysis of SURF-1 revealed mutations in numerous DNA samples from LD(COX-) patients, indicating that this gene is responsible for the major complementation group in this important mitochondrial disorder.
Emery and Rimoin's Principles and Practice of Medical Genetics
527 Citations1997David L. Rimoin
Nucleic Acids ResearchMITOMAP: a human mitochondrial genome database
522 Citations1996Andreas M. Kogelnik
FEBS LettersMitochondria and programmed cell death: back to the future
506 Citations1996Patrice X. Petit, Santos A. Susín +3 more
This work has shown that in vitro induction of permeability transition in isolated mitochondria provokes the release of a protein factor capable of inducing nuclear chromatin condensation and fragmentation, which prevents apoptosis.
Proceedings of the National Academy of SciencesMELAS mutation in mtDNA binding site for transcription termination factor causes defects in protein synthesis and in respiration but no change in levels of upstream and downstream mature transcripts.
497 Citations1992Anne Chomyn, Andrea Martinuzzi +8 more
The pathogenetic mechanism of the mitochondrial tRNA(LeuUUR) gene mutation responsible for the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome was investigated in transformants obtained by transfer of mitochondria from three genetically unrelated M ELAS patients into human mitochondrial DNA-less (rho 0) cells.
Nature GeneticsA novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase
494 Citations1998Simon Melov, Julie A. Schneider +6 more
PubMedHeteroplasmic mtDNA mutation (T----G) at 8993 can cause Leigh disease when the percentage of abnormal mtDNA is high.
484 Citations1992Y. Tatuch, John Christodoulou +7 more
Nature GeneticsTissue-specific selection for different mtDNA genotypes in heteroplasmic mice
454 Citations1997Jack P. Jenuth, Alan C. Peterson +1 more
Analysis of segregation of two different mtDNA genotypes in the tissues of heteroplasmic mice suggests that the coding sequence of mtDNA may represent a compromise between the competing demands of different tissues and point to the existence of unknown, tissue-specific nuclear genes important in the interaction between the nuclear and mitochondrial genomes.
Journal of Biological ChemistryIncreased Oxidative Damage Is Correlated to Altered Mitochondrial Function in Heterozygous Manganese Superoxide Dismutase Knockout Mice
454 Citations1998Melissa D. Williams, Holly Van Remmen +4 more
Substantial evidence is provided correlating reduced MnSOD activity in vivo to increased oxidative damage in mitochondria and alterations in mitochondrial function and direct evidence correlation to altered mitochondrial function is provided.
GenomicsMitochondrial DNA Variants Observed in Alzheimer Disease and Parkinson Disease Patients
447 Citations1993John M. Shoffner, Michael D. Brown +15 more
BiochemistryMitochondrial ADP/ATP Carrier Can Be Reversibly Converted into a Large Channel by Ca<sup>2+</sup>
423 Citations1996Nickolay Brustovetsky, Martin Klingenberg
The AAC, when converted into a large unselective channel, is a key component in the MTP and thus is involved in the ischemia-reperfusion damage and cytosolic Ca2+ oscillations.
Journal of Clinical InvestigationMitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase.
387 Citations1996Sari Pitkänen, B. H. Robinson
It is shown that the observed superoxide production rates are modulated by the variant induction of MnSOD which decreases the rates, sometimes below those seen in control fibroblast mitochondria, and it is most likely a function of the change in the redox state of the cell experienced rather than a result of the complex I defect per se.
Mutation Research/DNAgingAssociation of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease
364 Citations1992Marisol Corral‐Debrinski, John M. Shoffner +2 more
Observations support the hypothesis that mtDNA damage does accumulate with age and indicates that respiratory stress greatly elevates mitochondrial damage.
Proceedings of the National Academy of SciencesA mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber hereditary optic neuropathy and dystonia.
316 Citations1994A. S. Jun, M.D. Brown +1 more
A five-generation Hispanic family expressing maternally transmitted Leber hereditary optic neuropathy and/or early-onset dystonia associated with bilateral basal ganglia lesions was studied, and a unique mtDNA variant in Native American haplogroup D was found, suggesting that it is the disease-causing mutation.
GenomicsMarked Changes in Mitochondrial DNA Deletion Levels in Alzheimer Brains
311 Citations1994Marisol Corral‐Debrinski, Terzah M. Horton +6 more
The hypothesis that OXPHOS defects resulting from somatic mtDNA mutations may play a role in AD pathophysiology is supported.
Molecular and Cellular BiologyIn vitro genetic transfer of protein synthesis and respiration defects to mitochondrial DNA-less cells with myopathy-patient mitochondria.
295 Citations1991Anne Chomyn, G. Meola +4 more
A severe mitochondrial protein synthesis defect in myoblasts from a patient with mitochondrial myopathy was transferred with myoblast mitochondria into two genetically unrelated mitochondrial DNA-less human cell lines, pointing to an mtDNA alteration as being responsible and sufficient for causing the disease.
The American Journal of Human GeneticsThe First Nuclear-Encoded Complex I Mutation in a Patient with Leigh Syndrome
285 Citations1998Jan Loeffen, Jan Smeıtınk +8 more
The first molecular genetic link between a nuclear-encoded subunit of complex I and Leigh syndrome is described, and two compound heterozygous transitions in a patient with neuropathologically proven Leigh syndrome are described.
Nucleic Acids ResearchMarked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle
273 Citations1995Simon Melov, John M. Shoffner +2 more
The data imply that a wide spectrum of mtDNA rearrangements accumulate in old individuals, which correlates with the marked age related decrease in OXPHOS capacity observed in post-mitotic tissues.
The American Journal of Human GeneticsDemonstration of a New Pathogenic Mutation in Human Complex I Deficiency: A 5-bp Duplication in the Nuclear Gene Encoding the 18-kD (AQDQ) Subunit
264 Citations1998Lambert van den Heuvel, W. Ruitenbeek +8 more
A homozygous 5-bp duplication, destroying a consensus phosphorylation site, in the 18-kD cDNA was found in a complex I-deficient patient and the patient showed normal muscle morphology and a remarkably nonspecific fatal progressive phenotype without increased lactate concentrations in body fluids.
Journal of Biological ChemistryThe Protein Import System of Mitochondria
260 Citations1996Gottfried Schatz
Most of the information on mitochondrial protein import has come from studies in the yeast Saccharomyces cerevisiae and the mold Neurospora crassa, but it is likely that protein import into mammalian mitochondria occurs by very similar mechanisms.
CellDeletion mutants are functionally dominant over wild-type mitochondrial genomes in skeletal muscle fiber segments in mitochondrial disease
245 Citations1990Eric A. Shoubridge, George Karpati +1 more
The distribution and expression of wild-type and deleted mitochondrial DNA (mtDNA) molecules in skeletal muscle fibers of patients with mitochondrial disease are mapped and it is shown that ragged red fiber segments represent focal accumulations of mitochondria containing predominantly deleted mtDNAs and that the mutant genomes are absent or extremely rare in normal fiber segments.
Nature GeneticsAn autosomal locus predisposing to deletions of mitochondrial DNA
241 Citations1995Anu Suomalainen, Jyrki Kaukonen +7 more
The assignment of this disease locus to 10q 23.3–24.3 is the first direct evidence for involvement of both nuclear and mitochondrial genomes in a single disorder.
Proceedings of the National Academy of SciencesAncient mtDNA sequences in the human nuclear genome: A potential source of errors in identifying pathogenic mutations
233 Citations1997Douglas C. Wallace, Carol Stugard +3 more
Phylogenetic analysis of the nuclear CO1 and CO2 sequences revealed that they diverged from modern human mtDNAs early in hominid evolution about 770,000 years before present, consistent with the interpretation that the missense mutations proposed to cause AD may be the product of ancient mtDNA variants preserved as nuclear pseudogenes.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseMitochondrial diabetes mellitus: a review
220 Citations1995Klaus-Dieter Gerbitz, Johannes M.W. van den Ouweland +2 more
Phenotypically this type of mitochondrial diabetes is combined with deafness in more than 60% and is clinically distinguishable with respect to several characteristics from the two idiopathic forms of diabetes.
Proceedings of the National Academy of SciencesDetection of "deleted" mitochondrial genomes in cytochrome-c oxidase-deficient muscle fibers of a patient with Kearns-Sayre syndrome.
214 Citations1989Shuji Mita, Beny Schmidt +3 more
Using in situ hybridization and immunocytochemistry, a muscle biopsy sample from a patient with Kearns-Sayre syndrome who had a deletion of mitochondrial DNA and partial deficiency of cytochrome-c oxidase was studied to seek a relationship between COX deficiency and abnormalities of mtDNA at the single-fiber level.
Proceedings of the National Academy of SciencesCytoplasmic transfer of the mtDNA nt 8993 T-->G (ATP6) point mutation associated with Leigh syndrome into mtDNA-less cells demonstrates cosegregation with a decrease in state III respiration and ADP/O ratio.
191 Citations1994Ian A. Trounce, Stewart G. Neill +1 more
The reduced state III respiration rates and ADP/O ratios are linked to the T-->G mutation at nt 8993, suggesting a defective mitochondrial H(+)-translocating ATP synthase.
Proceedings of the National Academy of SciencesA mitochondrial DNA clone is associated with increased risk for Alzheimer disease.
186 Citations1995Tim Hutchin, Gino Cortopassi
Investigation of the notion that this mutation leads to excess risk of AD by using a case-control study design of 72 AD autopsies and 296 race- and age-matched controls finds that approximately 1.5 million Caucasians in the United States bear the 4336G mutation and are at significantly increased risk of developing mitochondrial AD in their lifetime.
Proceedings of the National Academy of SciencesCytoplasmic Inheritance of Chloramphenicol Resistance in Mouse Tissue Culture Cells
183 Citations1974Clive L. Bunn, Douglas C. Wallace +1 more
It is proposed, therefore, that chloramphenicol resistance is a cytoplasmically inherited characteristic in this mouse cell line.
Techniques in Somatic Cell Genetics
173 Citations1982Jerry W. Shay
Microbiological ReviewsStructure and evolution of organelle genomes
167 Citations1982Douglas C. Wallace
A comparison study of organelle Genome Evolution with a comparison of mitochondrial DNAs and chloroplast DNAs shows clear patterns of divergence patterns between organelle and nuclear DNAs.
The Journal of Cell BiologyCytoplasmic transfer of chloramphenicol resistance in human tissue culture cells.
165 Citations1975Douglas C. Wallace, Clive L. Bunn +1 more
It can be concluded that CAP resistance is coded in the cytoplasm and not in the nucleus of 296-1 cells, and this resistance can be transferred to cells of widely different origin and differentiated state.
Genes Chromosomes and CancerNovel mitochondrial DNA deletion found in a renal cell carcinoma
160 Citations1996Terzah M. Horton, John A. Petros +6 more
PCR was used to analyze a rarely deleted region of mitochondrial DNA from 39 human renal cell carcinomas (RCC) and matched normal kidney tissue removed during radical nephrectomy and revealed a 264 bp deletion in the first subunit (NDI) of NADH:ubiquinone oxidoreductase (complex I) of the electron transport chain.
Molecular and Cellular BiologyUse of Transmitochondrial Cybrids To Assign a Complex I Defect to the Mitochondrial DNA-Encoded NADH Dehydrogenase Subunit 6 Gene Mutation at Nucleotide Pair 14459 That Causes Leber Hereditary Optic Neuropathy and Dystonia
159 Citations1996Albert S. Jun, Ian A. Trounce +3 more
Observations suggest that the ND6 np 14459 mutation may alter the coenzyme Q-binding site of complex I, which is the cause of Leber hereditary optic neuropathy and/or pediatric-onset dystonia in three unrelated families.
OncogeneMicrosatellite instability in the mitochondrial DNA of colorectal carcinomas: Evidence for mismatch repair systems in mitochondrial genome
155 Citations1998Wataru Habano, Shinichi Nakamura +1 more
Results suggested that certain repair systems, like the mismatch repair systems in the nuclear genome, are required for mtDNA maintenance and that defects in these systems can lead to target mitochondrial gene mutations in colorectal carcinomas.
NeurologySubacute necrotizing encephalopathy
154 Citations1992John M. Shoffner, Paul M. Fernhoff +11 more
Three SNE pedigrees were evaluated biochemically for OXPHOS abnormalities and genetically for four mtDNA point mutations, and an mtDNA mutation in the ATPase, subunit 6 gene was present in one SNE pedigree.
NeurologyLeber's disease and dystonia
151 Citations1986Edward J. Novotny, Gurparkash Singh +5 more
A kindred in which 8 members had the neuroretinopathy of Leber's disease; 14 had a progressive, generalized dystonia attributed to striatal degeneration; and 1 had both disorders may be a mitochondrial disease.
GeneticsMitochondrial Genotype Segregation During Preimplantation Development in Mouse Heteroplasmic Embryos
130 Citations1998Flávio Vieira Meirelles, Lawrence C. Smith
The results suggest that heteroplasmy caused by polymorphic mitochondria positioned in the periphery of oocytes at the time of fertilization shows a more stringent segregation pattern than when the organelle is in the vicinity of the nucleus.
Biochemical and Biophysical Research CommunicationsDetection of hydroxyl radical in the mitochondria of ischemic-reperfused myocardium by trapping with salicylate
124 Citations1989Dipak K. Das, Anna George +2 more
The results indicated for the first time the presence of hydroxyl radical in the mitochondrial fraction during early reperfusion, which decreased in intensity as the reperfusions progressed.
PubMedNuclear complementation restores mtDNA levels in cultured cells from a patient with mtDNA depletion.
118 Citations1993A G Bodnar, Jonathan M. Cooper +3 more
Results indicate that mtDNA depletion in a patient with a fatal mitochondrial disease manifesting soon after birth is under the control of the nuclear genome.
Annals of NeurologyLeber's hereditary optic neuropathy plus dystonia is caused by a mitochondrial DNA point mutation
113 Citations1995John M. Shoffner, Michael D. Brown +11 more
Nucleic Acids ResearchMulti-Organ Characterization of Mitochondrial Genomic Rearrangements in Ad Libitum and Caloric Restricted Mice Show Striking Somatic Mitochondrial DNA Rearrangements with Age
112 Citations1997Simon Melov, Douglas Hinerfeld +2 more
Observations confirm that mtDNA mutations accumulate with age in mice and suggest that caloric restriction impedes this progress, which is suggested to extend life span supporting an association between bioenergetics and senescence.
Molecular and Cellular BiologyIn Vitro Analysis of Mutations Causing Myoclonus Epilepsy with Ragged-Red Fibers in the Mitochondrial tRNA<sup>Lys</sup> Gene: Two Genotypes Produce Similar Phenotypes
112 Citations1995Judy P. Masucci, Mercy M. Davidson +3 more
It is demonstrated that two different mtDNA mutations in tRNA(Lys), both associated with the same mitochondrial disorder, result in fundamentally identical defects at the cellular level and strongly suggest that specific protein synthesis abnormalities contribute to the pathogenesis of myoclonus epilepsy with ragged-red fibers.
Mutation Research/DNAgingProgressive loss of cytochrome c oxidase in the human extraocular muscles in ageing — a cytochemical-immunohistochemical study
111 Citations1992Josef Müller‐Höcker, Karin Schneiderbanger +2 more
The loss of both mitochondrial and nuclear subunits indicates that nuclear factors are most probably involved in the decline of the respiratory chain function in senescence.
Journal of Biological ChemistryMitochondrial DNA expression in mitochondrial myopathies and coordinated expression of nuclear genes involved in ATP production
109 Citations1993Abdelaziz Heddi, Patrick Lestienne +2 more
The results demonstrate that the expression of nuclear and cytoplasmic OX PHOS genes is coordinated and that OXPHOS gene expression increases to compensate for respiratory deficiency and the repression of nuclear genes in KSS muscle could be a consequence of the segmental distribution of deleted mtDNA molecules in muscle cells.
NeurologyMarked increase in mitochondrial DNA deletion levels in the cerebral cortex of Huntington's disease patients
108 Citations1995Terzah M. Horton, Brett H. Graham +5 more
The hypothesis that HD is associated with elevated cortical mtDNA damage is supported by the quantitated amount of the common mitochondrial 4977 nucleotide pair deletion in cortex and putamen of HD patients and age-matched controls by the serial dilution-polymerase chain reaction method.
Transgenic ResearchMitochondria transfer into mouse ova by microinjection
103 Citations1997Carl A. Pinkert, Michael H. Irwin +2 more
A method for mitochondria isolation and interspecific transfer of mitochondria was developed in mice and high rates of successful transfer of foreign mitochondria were revealed after isolation and injection into zygotes cultured through the blastocyst stage of embryonic development.
Muscle & NerveClinical features of melas and mitochondrial DNA mutations
96 Citations1995Yu‐ichi Goto
It is worthwhile to summarize the clinical and pathological findings and to prove the discrepancy between phenotype and genotype and to start a starting point for further discussion of the pathomechanism and so toward further understanding of the disease itself.
Annals of NeurologyMolecular genetic characterization of an X‐linked form of Leigh's syndrome
84 Citations1993Paul M. Matthews, David R. Marchington +4 more
Observance that the Elα subunit is encoded on the X chromosome confirms that some patients with Leigh's syndrome may potentially exhibit X‐linked inheritance.
Archives of OphthalmologyVariable Retinal and Neurologic Manifestations in Patients Harboring the Mitochondrial DNA 8993 Mutation
79 Citations1993Rafael G. Ortiz
Proceedings of the National Academy of SciencesTeratocarcinoma cells as vehicles for introducing specific mutant mitochondrial genes into mice
47 Citations1978Tomomasa Watanabe, Michael J. Dewey +1 more
Teratocarcinoma cybrids offer a practical portal of entry of preselected mitochondrial genes into mice and will ultimately permit in vivo investigation of maternally transmitted traits, of mitochondrial genetic influences in specialized cells, and of possible roles of cytoplasmic genes in clinical and disease states.
Muscle & NerveSuperoxide dismutases of muscle in mitochondrial encephalomyopathies
39 Citations1995Norio Ohkoshi, H Mizusawa +4 more
It is suggested that Mn‐SOD‐positive fibers can be used to make a differential diagnosis between CPEO and MELAS and that in mitochondrial encephalomyopathies Mn-SOD in the raggedred fibers may protect against oxidative stress.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseSteady state levels of mitochondrial and nuclear oxidative phosphorylation transcripts in Kearns-Sayre syndrome
34 Citations1994Abdelaziz Heddi, Patrick Lestienne +2 more
The steady state levels of both mitochondrial and nuclear transcripts were examined in a Kearns-Sayre syndrome patient harboring a heteroplasmic 7.7 kb mitochondrial DNA deletion and RNA levels from three nuclear genes encoding two of the Adenine Nucleotide Translocator isoforms and the beta subunit of the ATPsynthase were significantly induced in the different tissues independently of the percentage of deleted mtDNA molecules.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseSearching for genes affecting the structural integrity of the mitochondrial genome
30 Citations1995Massimo Zeviani, Patrizia Amati +4 more
Linkage analysis and search for candidate genes are two complementary strategies aimed at identifying the genes responsible for these disorders.
Cytoplasmic Inheritance of Chloramphenicol Resistance in Mammalian Cells
20 Citations1982Douglas C. Wallace
Chloramphenicol resistance was the first cytoplasmic drug resistance marker to be described for mammalian cells and a variety of structurally related analogs are potent inhibitors of both bacteria and mammalian cells.
…