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824 results on '"Turnbull, Douglass M."'

51. An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy

Author

Clark, Kim M., Taylor, Robert W., Johnson, Margaret A., Chinnery, Patrick F., Chrzanowska-Lightowlers, Zofia M.A., Andrews, Richard M., Nelson, Isobel P., Wood, Nicholas W., Lamont, Phillipa J., Hanna, Michael G., Lightowlers, Robert N., and Turnbull, Douglass M.

Subjects
Genetic disorders -- Research, Chromosome mapping -- Usage, Mitochondrial DNA -- Physiological aspects, Mitochondrial myopathies -- Genetic aspects, Encephalopathy -- Genetic aspects, Biological sciences
Abstract

A family with mitochondrial disease was found to have an mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II (COX II) gene. The mutation brings lower levels of the protein and a mitochondrial encephalomyopathy. It is predicted that the T-->C transition changes the initiating methionine to threonine. The mutation load was at 67% in muscle from the index case and at 91% in muscle from the clinically affected son of the patient. An isolated COX deficiency was seen in muscle biopsy samples. The mutation is a new mechanism through which mtDNA mutations can cause disease-defective translation initiation.

Published
1999

59. Naked mole-rats maintain healthy skeletal muscle and Complex IV mitochondrial enzyme function into old age

Author

Stoll, Elizabeth A, Karapavlovic, Nevena, Rosa, Hannah, Woodmass, Michael, Rygiel, Karolina, White, Kathryn, Turnbull, Douglass M, and Faulkes, Chris G

Subjects
Male, Aging, Electron Transport Complex I, naked mole-rat, Mole Rats, mitochondria, sarcopenia, Electron Transport Complex IV, Muscular Atrophy, oxidative stress, animal models of aging, Animals, Muscle, Skeletal, Research Paper
Abstract

The naked mole-rat (NMR) Heterocephalus glaber is an exceptionally long-lived rodent, living up to 32 years in captivity. This extended lifespan is accompanied by a phenotype of negligible senescence, a phenomenon of very slow changes in the expected physiological characteristics with age. One of the many consequences of normal aging in mammals is the devastating and progressive loss of skeletal muscle, termed sarcopenia, caused in part by respiratory enzyme dysfunction within the mitochondria of skeletal muscle fibers. Here we report that NMRs avoid sarcopenia for decades. Muscle fiber integrity and mitochondrial ultrastructure are largely maintained in aged animals. While mitochondrial Complex IV expression and activity remains stable, Complex I expression is significantly decreased. We show that aged naked mole-rat skeletal muscle tissue contains some mitochondrial DNA rearrangements, although the common mitochondrial DNA deletions associated with aging in human and other rodent skeletal muscles are not present. Interestingly, NMR skeletal muscle fibers demonstrate a significant increase in mitochondrial DNA copy number. These results have intriguing implications for the role of mitochondria in aging, suggesting Complex IV, but not Complex I, function is maintained in the long-lived naked mole rat, where sarcopenia is avoided and healthy muscle function is maintained for decades.

Published
2016

63. Assessing mitochondrial heteroplasmy using next generation sequencing: A note of caution

Author

Santibanez-Koref, Mauro, Griffin, Helen, Turnbull, Douglass M., Chinnery, Patrick F., Herbert, Mary, and Hudson, Gavin

Subjects
Mitochondrial Diseases, Computational Biology, Genetic Variation, High-Throughput Nucleotide Sequencing, Humans, Sequence Analysis, DNA, DNA, Mitochondrial, Article
Abstract

The mitochondrial genome has recently become the focus of several high-impact next-generation sequencing studies investigating the effect of mutations in disease and assessing the efficacy of mitochondrial replacement therapies. However, these studies have failed to take into consideration the capture of recurring translocations of mitochondrial DNA to the nuclear genome, known as nuclear mitochondrial sequences (NUMTs), continuing to align sequence data to the revised Cambridge reference sequence alone. Here, using different mtDNA enrichment techniques and a variety of tissues, we demonstrate that NUMTs are present in sequence data and that, dependent upon downstream analysis, are at a level which affects variant calling.

Published
2019

64. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease

Author

Gorman, Gráinne S, Schaefer, Andrew M, Ng, Yi, Gomez, Nicholas, Blakely, Emma L, Alston, Charlotte L, Feeney, Catherine, Horvath, Rita, Yu-Wai-Man, Patrick, Chinnery, Patrick F, Taylor, Robert W, Turnbull, Douglass M, McFarland, Robert, Horvath, Rita [0000-0002-9841-170X], Yu Wai Man, Patrick [0000-0001-7847-9320], Chinnery, Patrick [0000-0002-7065-6617], and Apollo - University of Cambridge Repository

Subjects
Adult, Cell Nucleus, Young Adult, Cross-Sectional Studies, Mitochondrial Diseases, England, Mutation, Prevalence, Humans, DNA, Mitochondrial
Abstract

OBJECTIVE: The prevalence of mitochondrial disease has proven difficult to establish, predominantly as a result of clinical and genetic heterogeneity. The phenotypic spectrum of mitochondrial disease has expanded significantly since the original reports that associated classic clinical syndromes with mitochondrial DNA (mtDNA) rearrangements and point mutations. The revolution in genetic technologies has allowed interrogation of the nuclear genome in a manner that has dramatically improved the diagnosis of mitochondrial disorders. We comprehensively assessed the prevalence of all forms of adult mitochondrial disease to include pathogenic mutations in both nuclear and mtDNA. METHODS: Adults with suspected mitochondrial disease in the North East of England were referred to a single neurology center from 1990 to 2014. For the midyear period of 2011, we evaluated the minimum prevalence of symptomatic nuclear DNA mutations and symptomatic and asymptomatic mtDNA mutations causing mitochondrial diseases. RESULTS: The minimum prevalence rate for mtDNA mutations was 1 in 5,000 (20 per 100,000), comparable with our previously published prevalence rates. In this population, nuclear mutations were responsible for clinically overt adult mitochondrial disease in 2.9 per 100,000 adults. INTERPRETATION: Combined, our data confirm that the total prevalence of adult mitochondrial disease, including pathogenic mutations of both the mitochondrial and nuclear genomes (≈1 in 4,300), is among the commonest adult forms of inherited neurological disorders. These figures hold important implications for the evaluation of interventions, provision of evidence-based health policies, and planning of future services.

Published
2019
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78. Mitochondrial DNA mutations in human colonic crypt stem cells

Author

Taylor, Robert W., Barron, Martin J., Borthwick, Gillian M., Gospel, Amy, Chinnery, Patrick F., Samuels, David C., Taylor, Geoffrey A., Plusa, Stefan M., Needham, Stephanie J., Greaves, Laura C., Kirkwood, Thomas B.L., and Turnbull, Douglass M.

Published
2003

89. Mitochondrial DNA Transcription: Regulating the Power Supply

Author

Taylor, Robert W. and Turnbull, Douglass M.

Subjects
Mitochondrial DNA, Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2007.07.002 Byline: Robert W. Taylor (1)(2), Douglass M. Turnbull (1)(2)(3) Abstract: In this issue of Cell, describe the nuclear encoded protein MTERF3 as a negative regulator of mitochondrial DNA transcription initiation. This study highlights a mechanism by which mitochondrial DNA transcription (and therefore oxidative phosphorylation) may be regulated in response to alterations in the cell's physiological and metabolic demands. Author Affiliation: (1) Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, Newcastle University, Newcastle upon Tyne, UK (2) Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK (3) Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK

Published
2007

90. Sub-cellular origin of mtDNA deletions in human skeletal muscle

Author

Vincent, Amy E., Rosa, Hannah S., Pabis, Kamil, Lawless, Conor, Chen, Chun, Grunewald, Anne, Rygiel, Karolina A., Rocha, Mariana C., Reeve, Amy K., Falkous, Gavin, Perissi, Vanessa, White, Kathryn, Davey, Tracey, Petrof, Basil J., Sayer, Avan Aihie, Cooper, Cyrus, Deehan, David, Taylor, Robert W., Turnbull, Douglass M., and Picard, Martin

Published
2018

91. Opening One's Eyes to Mosaicism in Progressive External Ophthalmoplegia

Author

Sommerville, Ewen W., Jones, Rachel L., Hardy, Steven A., Blakely, Emma L., Pyle, Angela, Schaefer, Andrew M., Chinnery, Patrick F., Turnbull, Douglass M., Gorman, Gráinne S., Taylor, Robert W., Chinnery, Patrick [0000-0002-7065-6617], and Apollo - University of Cambridge Repository

Subjects
3209 Neurosciences, 32 Biomedical and Clinical Sciences, Clinical/Scientific Notes, 3202 Clinical Sciences, 3105 Genetics, 31 Biological Sciences
Published
2018
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92. Impact of age-related mitochondrial dysfunction and exercise on intestinal microbiota composition

Author

Houghton, David, Stewart, Christopher J, Stamp, Craig, Nelson, Andrew, Aj ami, Nadim J, Petrosino, Joseph F, Wipat, Anil, Trenell, Michael I, Turnbull, Douglass M, and Greaves, Laura C

Subjects
Aging, Mitochondrial Diseases, C100, A100, D300, Articles, Gut microbiota, C500, B400, C700, digestive system, Mitochondria, Gastrointestinal Microbiome, Feces, Mice, Random Allocation, Physical Conditioning, Animal, The Journal of Gerontology: Biological Sciences, COX deficiency, Animals, Sedentary Behavior, Exercise
Abstract

Mitochondrial dysfunction is prevalent in the aging gastrointestinal tract. We investigated whether mitochondrial function in aging colonic crypts and exercise influences microbial gut communities in mice. Twelve PolgAmut/mut mice were randomly divided into a sedentary and exercise group at 4 months. Seven-aged matched PolgA+/+ mice remained sedentary throughout. Stool samples were collected at 4, 7, and 11 months, and bacterial profiling was achieved through 16S rRNA sequencing profiling. Mitochondrial enzyme activity was assessed in colonic epithelial crypts at 11 months for PolgAmut/mut and PolgA+/+ mice. Sedentary and exercised PolgAmut/mut mice had significantly higher levels of mitochondrial dysfunction than PolgA+/+ mice (78%, 77%, and 1% of crypts, respectively). Bacterial profiles of sedentary PolgAmut/mut mice were significantly different from the sedentary PolgA+/+ mice, with increases in Lactobacillus and Mycoplasma, and decreases in Alistipes, Odoribacter, Anaeroplasma, Rikenella, Parabacteroides, and Allobaculum in the PolgAmut/mut mice. Exercise did not have any impact upon gut mitochondrial dysfunction; however, exercise did increase gut microbiota diversity and significantly increased bacterial genera Mucispirillum and Desulfovibrio. Mitochondrial dysfunction is associated with changes in the gut microbiota. Endurance exercise moderated some of these changes, establishing that environmental factors can influence gut microbiota, despite mitochondrial dysfunction.

Published
2018

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