Navegando por Palavras-chave "mtDNA"
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- ItemAcesso aberto (Open Access)Duplication and triplication with staggered breakpoints in human mitochondrial DNA(Elsevier B.V., 1998-02-27) Tengan, Célia Harumi [UNIFESP]; Moraes, Carlos Torres; Univ Miami; Universidade Federal de São Paulo (UNIFESP)We identified a tandem duplication and triplication of a mitochondrial DNA (mtDNA) segment in the muscle of a 57-year-old man with no evidence of a neuromuscular disorder. A large triplication of a mtDNA coding region has not been previously reported in humans. Furthermore, the rearrangements (comprising 10-12% of the muscle mtDNA pool in the propositus) were unique because the breakpoints were staggered at both ends (between mtDNA positions 3263-3272 and 16065-16076) and contained no identifiable direct repeats. Both sides of the breakpoint were located approximately 35 bp downstream of regions that undergo frequent strand displacement by either transcription (positions 3263-3272) or replication (positions 16065-16076), suggesting that topological changes generated by the movement of RNA/DNA polymerases may be associated with the genesis of a subclass of mtDNA rearrangements. the presence of low levels of these rearrangements in other normal adults also suggest that these mutations are not rare. the characterization of these rearrangements shed light on potential alternative mechanisms for the genesis of mtDNA rearrangements. (C) 1998 Elsevier Science B.V.
- ItemAcesso aberto (Open Access)Evidence for Mitochondrial Genome Methylation in the Yeast Candida albicans: A Potential Novel Epigenetic Mechanism Affecting Adaptation and Pathogenicity?(Frontiers Media Sa, 2018) Bartelli, Thais Fernanda [UNIFESP]; Bruno, Danielle C. F.; Briones, Marcelo Ribeiro da Silva [UNIFESP]The commensal yeast Candida albicans is an opportunistic pathogen. In order to successfully colonize or infect the human body, the fungus must adapt to the host's environmental conditions, such as low oxygen tension (hypoxia), temperature (37 degrees C), and the different carbon sources available. Previous studies demonstrated the adaptive importance of C. albicans genetic variability for its pathogenicity, although the contributions of epigenetic and the influence of environmental factors are not fully understood. Mitochondria play important roles in fungal energetic metabolism, regulation of nuclear epigenetic mechanisms and pathogenicity. However, the specific impact of inter-strain mitochondrial genome variability and mitochondrial epigenetics in pathogenicity is unclear. Here, we draw attention to this relevant organelle and its potential role in C. albicans pathogenicity and provide preliminary evidence, for the first time, for methylation of the yeast mitochondrial genome. Our results indicate that environmental conditions, such as continuous exposure for 12 weeks to hypoxia and 37 degrees C, decrease the mitochondrial genome methylation in strains SC5314 and L757. However, the methylation decrease is quantitatively different in specific genome positions when strains SC5314 and L757 are compared. We hypothesize that this phenomenon can be promising for future research to understand how physical factors of the host affect the C. albicans mitochondrial genome and its possible impact on adaptation and pathogenicity.
- ItemAcesso aberto (Open Access)Mitochondrial DNA damage associated with lipid peroxidation of the mitochondrial membrane induced by Fe2+-citrate(Academia Brasileira de Ciências, 2006-09-01) Almeida, Andréa M.; Bertoncini, Clelia Rejane Antonio [UNIFESP]; Borecký, Jiri; Souza-Pinto, Nadja C.; Vercesi, Aníbal E.; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Viçosa Departamento de Biologia Vegetal; National Institute on Aging Laboratory of Molecular GerontologyIron imbalance/accumulation has been implicated in oxidative injury associated with many degenerative diseases such as hereditary hemochromatosis, beta-thalassemia, and Friedreich's ataxia. Mitochondria are particularly sensitive to iron-induced oxidative stress - high loads of iron cause extensive lipid peroxidation and membrane permeabilization in isolated mitochondria. Here we detected and characterized mitochondrial DNA damage in isolated rat liver mitochondria exposed to a Fe2+-citrate complex, a small molecular weight complex. Intense DNA fragmentation was induced after the incubation of mitochondria with the iron complex. The detection of 3' phosphoglycolate ends at the mtDNA strand breaks by a 32P-postlabeling assay, suggested the involvement of hydroxyl radical in the DNA fragmentation induced by Fe2+-citrate. Increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine also suggested that Fe2+-citrate-induced oxidative stress causes mitochondrial DNA damage. In conclusion, our results show that iron-mediated lipid peroxidation was associated with intense mtDNA damage derived from the direct attack of reactive oxygen species.
- ItemSomente MetadadadosThe mutations m.5628T > C and m18348A > G in single muscle fibers of a patient with chronic progressive external ophthalmoplegia(Elsevier B.V., 2012-09-15) Gamba, Juliana [UNIFESP]; Kiyomoto, Beatriz Hitomi [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; Gabbai, Alberto Alain [UNIFESP]; Schmidt, Beny [UNIFESP]; Tengan, Celia Harumi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)We identified a double mutation in a patient with chronic progressive external ophthalmoplegia, located in the tRNA(Ala) (m.5628T > C) and tRNA(LYs) (m.8348A > G) genes. Both mutations were previously described separately and considered pathogenic, however the same mutations were also reported as polymorphisms or phenotype modulator. We analyzed the proportion of each mutation in isolated muscle fibers by single fiber-polymerase chain reaction to investigate the contribution of each mutation to mitochondrial deficiency. Our findings demonstrated that the mutations were heteroplasmic in skeletal muscle and both mutations were present in all single muscle fibers. the proportions of the m.5628T > C mutation were not significantly different between normal and cytochrome-c-oxidase (COX) deficient fibers. However, a significant higher proportion of the m.8348A > G mutation was observed in COX deficient fibers. Homoplasmic m.8348A > G was only observed in COX negative fibers. in conclusion, we provide a piece of evidence toward the pathogenicity of the m.8348A > G mutation and suggest that m.5628T > C is probably a neutral polymorphism. (c) 2012 Elsevier B.V. All rights reserved.