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https://www.readbyqxmd.com/read/27926991/human-mitochondrial-nucleases
#1
REVIEW
Francesco Bruni, Robert N Lightowlers, Zofia M Chrzanowska-Lightowlers
Mitochondria are cytosolic organelles that have many essential roles including ATP production via oxidative phosphorylation, apoptosis, iron-sulphur cluster biogenesis, heme and steroid synthesis, calcium homeostasis and regulation of cellular redox state. One of the unique features of these organelles is the presence of an extra-chromosomal mitochondrial genome (mtDNA), together with all the machinery required to replicate and transcribe mtDNA. The accurate maintenance of mitochondrial gene expression is essential for correct organellar metabolism, and is in part dependent on the levels of mtDNA and mt-RNA, which are regulated by balancing synthesis against degradation...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27923980/humanin-skeletal-muscle-protein-levels-increase-after-resistance-training-in-men-with-impaired-glucose-metabolism
#2
Eva-Karin Gidlund, Ferdinand von Walden, Mika Venojärvi, Ulf Risérus, Olli J Heinonen, Jessica Norrbom, Carl Johan Sundberg
Humanin (HN) is a mitochondrially encoded and secreted peptide linked to glucose metabolism and tissue protecting mechanisms. Whether skeletal muscle HN gene or protein expression is influenced by exercise remains unknown. In this intervention study we show, for the first time, that HN protein levels increase in human skeletal muscle following 12 weeks of resistance training in persons with prediabetes. Male subjects (n = 55) with impaired glucose regulation (IGR) were recruited and randomly assigned to resistance training, Nordic walking or a control group...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/27923120/long-oskar-controls-mitochondrial-inheritance-in-drosophila-melanogaster
#3
Thomas Ryan Hurd, Beate Herrmann, Julia Sauerwald, Justina Sanny, Markus Grosch, Ruth Lehmann
Inherited mtDNA mutations cause severe human disease. In most species, mitochondria are inherited maternally through mechanisms that are poorly understood. Genes that specifically control the inheritance of mitochondria in the germline are unknown. Here, we show that the long isoform of the protein Oskar regulates the maternal inheritance of mitochondria in Drosophila melanogaster. We show that, during oogenesis, mitochondria accumulate at the oocyte posterior, concurrent with the bulk streaming and churning of the oocyte cytoplasm...
December 5, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27922635/increased-plasma-levels-of-circulating-cell-free-mitochondrial-dna-in-suicide-attempters-associations-with-hpa-axis-hyperactivity
#4
D Lindqvist, J Fernström, C Grudet, L Ljunggren, L Träskman-Bendz, L Ohlsson, Å Westrin
Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922198/dnmt1-modulation-in-chronic-hepatitis-b-patients-and-hypothetic-influence-on-mitochondrial-dna-methylation-status-during-long-term-nucleo-t-side-analogues-therapy
#5
Giordano Madeddu, Silvia Ortu, Giovanni Garrucciu, Ivana Maida, Michela Melis, Alberto Augusto Muredda, Maria Stella Mura, Sergio Babudieri
Inhibition of viral replication is the most important goal in patients with Hepatitis B virus chronic infection (CHB). Currently, five oral nucleo(t)side analogues (NAs), including Lamivudine, Adefovir, Telbivudine, Entecavir and Tenofovir, have been approved for treatment. The widespread use of NAs has also been linked with a progressive growth of unlikely anomaly attributable to mitochondrial dysfunctions, not previously recognized. Here we explore the hypothesis that NAs may cause persistent epigenetic changes during prolonged NAs therapy in CHB patients...
December 6, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/27921220/increased-cell-free-mitochondrial-dna-is-a-marker-of-ongoing-inflammation-and-better-neurocognitive-function-in-virologically-suppressed-hiv-infected-individuals
#6
Josué Pérez-Santiago, Michelli F De Oliveira, Susanna R Var, Tyler R C Day, Steven P Woods, Sara Gianella, Sanjay R Mehta
Cell-free mitochondrial DNA (mtDNA) is a highly immunogenic molecule that is associated with several inflammatory conditions and with neurocognitive impairment during untreated HIV infection. Here, we investigate how cell-free mtDNA in cerebrospinal fluid (CSF) is associated with inflammation, neuronal damage, and neurocognitive functioning in the context of long-term suppressive antiretroviral therapy (ART). We quantified the levels of cell-free mtDNA in the CSF from 41 HIV-infected individuals with completely suppressed HIV RNA levels in blood plasma (<50 copies/mL) by droplet digital PCR...
December 5, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27919866/mitochondrial-dna-haplogroups-influence-the-risk-of-incident-knee-osteoarthritis-in-oai-and-check-cohorts-a-meta-analysis-and-functional-study
#7
Mercedes Fernández-Moreno, Angel Soto-Hermida, María E Vázquez-Mosquera, Estefanía Cortés-Pereira, Sara Relaño, Tamara Hermida-Gómez, Sonia Pértega, Natividad Oreiro-Villar, Carlos Fernández-López, Rafael Garesse, Francisco J Blanco, Ignacio Rego-Pérez
OBJECTIVE: To evaluate the influence of the mitochondrial DNA (mtDNA) haplogroups in the risk of incident knee osteoarthritis (OA) and to explain the functional consequences of this association to identify potential diagnostic biomarkers and therapeutic targets. METHODS: Two prospective cohorts contributed participants. The osteoarthritis initiative (OAI) included 2579 subjects of the incidence subcohort, and the cohort hip and cohort knee (CHECK) included 635, both with 8-year follow-up...
December 5, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27919073/mitochondrial-replacement-in-human-oocytes-carrying-pathogenic-mitochondrial-dna-mutations
#8
Eunju Kang, Jun Wu, Nuria Marti Gutierrez, Amy Koski, Rebecca Tippner-Hedges, Karen Agaronyan, Aida Platero-Luengo, Paloma Martinez-Redondo, Hong Ma, Yeonmi Lee, Tomonari Hayama, Crystal Van Dyken, Xinjian Wang, Shiyu Luo, Riffat Ahmed, Ying Li, Dongmei Ji, Refik Kayali, Cengiz Cinnioglu, Susan Olson, Jeffrey Jensen, David Battaglia, David Lee, Diana Wu, Taosheng Huang, Don P Wolf, Dmitry Temiakov, Juan Carlos Izpisua Belmonte, Paula Amato, Shoukhrat Mitalipov
Maternally inherited mitochondrial (mt)DNA mutations can cause fatal or severely debilitating syndromes in children, with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type mtDNA (heteroplasmy) in each cell and tissue. Pathogenic mtDNA mutations are relatively common, with an estimated 778 affected children born each year in the United States. Mitochondrial replacement therapies or techniques (MRT) circumventing mother-to-child mtDNA disease transmission involve replacement of oocyte maternal mtDNA...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27917773/mutations-of-mtdna-polymerase-%C3%AE-and-hyperlactataemia-in-the-hiv-infected-zulu-population-of-south-africa
#9
D B A Ojwach, C Aldous, P Kochleff, B Sartorius
BACKGROUND: Mitochondrial toxicity, particularly symptomatic hyperlactataemia or lactic acidosis (SHL/LA), has been attributed to the use of nucleoside reverse transcriptase inhibitors (NRTIs), possibly because of their capacity to impede human mitochondrial DNA polymerase-γ (POLG), which is responsible for the replication of mitochondrial DNA. OBJECTIVE: To determine whether known monogenic POLG1 polymorphisms could be linked with the unexpectedly high incidence of SHL/LA observed in HIV-infected Zulu-speaking patients exposed to the NRTIs stavudine or zidovudine in their antiretroviral therapy...
December 1, 2016: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/27917263/changes-in-cellular-proliferation-and-plasma-products-are-associated-with-liver-failure
#10
Juliana Gil Melgaço, Frederico Marianetti Soriani, Pedro Henrique Ferreira Sucupira, Leonardo Assaf Pinheiro, Yasmine Rangel Vieira, Jaqueline Mendes de Oliveira, Lia Laura Lewis-Ximenez, Cristina Carvalho Vianna Araújo, Lúcio Filgueiras Pacheco-Moreira, Gustavo Batista Menezes, Oswaldo Gonçalves Cruz, Claudia Lamarca Vitral, Marcelo Alves Pinto
AIM: To study the differences in immune response and cytokine profile between acute liver failure and self-limited acute hepatitis. METHODS: Forty-six patients with self-limited acute hepatitis (AH), sixteen patients with acute liver failure (ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR...
November 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27916687/a-unique-combination-of-micronutrients-rejuvenates-cognitive-performance-in-aged-mice
#11
Sam D Perez, Kristy Du, Catarina Rendeiro, Lin Wang, Qian Wu, Stanislav S Rubakhin, Rema Vazhappilly, Jeffrey H Baxter, Jonathan V Sweedler, Justin S Rhodes
It is widely believed that diet can influence the onset and severity of cognitive aging, but the optimal combination of micronutrients and molecular and cellular mechanisms remain elusive. The purpose of this study was to compare the effects of eight distinct diets, consisting of various concentrations of selected micronutrients, on learning and memory as well as markers of neuronal plasticity, and metabolic and neuro-immune status of the aged hippocampus. Eighteen-month-old male and female C57BL/6J mice were fed the diets for 16 weeks, followed by learning and memory trials on the active avoidance task...
December 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27915089/complete-mitochondrial-genome-of-parasitic-nematode-cylicocyclus-nassatus-and-comparative-analyses-with-cylicocyclus-insigne
#12
Yuan Gao, Jian-Hua Qiu, Bing-Bing Zhang, Xin Su, Xue Fu, Dong-Mei Yue, Chun-Ren Wang
Cylicocyclus nassatus is a common and important parasite in the large intestine of equine. In this study, the complete mitochondrial (mt) genome sequence of C. nassatus was determined and comparatively analysed with Cylicocyclus insigne. The mt genome size of C. nassatus was 13,846 bp, 18 bp longer than that of C. insigne. The circular mt genome includes 12 protein-coding genes, two rRNA genes, 22 tRNA genes and two non-coding regions. All the genes are transcribed in the same direction and gene arrangement is consistent with that of gene arrangement 3 (GA3)...
November 30, 2016: Experimental Parasitology
https://www.readbyqxmd.com/read/27915046/dna-damage-related-crosstalk-between-the-nucleus-and-mitochondria
#13
Mohammad Saki, Aishwarya Prakash
The electron transport chain is the primary pathway by which a cell generates energy in the form of ATP. Byproducts of this process produce reactive oxygen species that can cause damage to mitochondrial DNA. If not properly repaired, the accumulation of DNA damage can lead to mitochondrial dysfunction linked to several human disorders including neurodegenerative diseases and cancer. Mitochondria are able to combat oxidative DNA damage via repair mechanisms that are analogous to those found in the nucleus. Of the repair pathways currently reported in the mitochondria, the base excision repair pathway is the most comprehensively described...
November 30, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27911443/transient-mitochondrial-dna-double-strand-breaks-in-mice-cause-accelerated-aging-phenotypes-in-a-ros-dependent-but-p53-p21-independent-manner
#14
Milena Pinto, Alicia M Pickrell, Xiao Wang, Sandra R Bacman, Aixin Yu, Aline Hida, Lloye M Dillon, Paul D Morton, Thomas R Malek, Siôn L Williams, Carlos T Moraes
We observed that the transient induction of mtDNA double strand breaks (DSBs) in cultured cells led to activation of cell cycle arrest proteins (p21/p53 pathway) and decreased cell growth, mediated through reactive oxygen species (ROS). To investigate this process in vivo we developed a mouse model where we could transiently induce mtDNA DSBs ubiquitously. This transient mtDNA damage in mice caused an accelerated aging phenotype, preferentially affecting proliferating tissues. One of the earliest phenotypes was accelerated thymus shrinkage by apoptosis and differentiation into adipose tissue, mimicking age-related thymic involution...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27908235/pentatricopeptide-motifs-in-the-n-terminal-extension-domain-of-yeast-mitochondrial-rna-polymerase-rpo41p-are-not-essential-for-its-function
#15
J Kruszewski, P Golik
The core mitochondrial RNA polymerase is a single-subunit enzyme that in yeast Saccharomyces cerevisiae is encoded by the nuclear RPO41 gene. It is an evolutionary descendant of the bacteriophage RNA polymerases, but it includes an additional unconserved N-terminal extension (NTE) domain that is unique to the organellar enzymes. This domain mediates interactions between the polymerase and accessory regulatory factors, such as yeast Sls1p and Nam1p. Previous studies demonstrated that deletion of the entire NTE domain results only in a temperature-dependent respiratory deficiency...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27908231/the-mitochondrial-genome-the-nucleoid
#16
REVIEW
A A Kolesnikov
Mitochondrial DNA (mtDNA) in cells is organized in nucleoids containing DNA and various proteins. This review discusses questions of organization and structural dynamics of nucleoids as well as their protein components. The structures of mt-nucleoid from different organisms are compared. The currently accepted model of nucleoid organization is described and questions needing answers for better understanding of the fine mechanisms of the mitochondrial genetic apparatus functioning are discussed.
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27908228/detection-of-mutations-in-mitochondrial-dna-by-droplet-digital-pcr
#17
J K Sofronova, Y Y Ilinsky, K E Orishchenko, E G Chupakhin, E A Lunev, I O Mazunin
Mutations in mitochondrial DNA (mtDNA) may result in various pathological processes. Detection of mutant mtDNAs is a problem for diagnostic practice that is complicated by heteroplasmy - a phenomenon of the inferring presence of at least two allelic variants of the mitochondrial genome. Also, the level of heteroplasmy largely determines the profile and severity of clinical manifestations. Here we discuss detection of mutations in heteroplasmic mtDNA using up-to-date methods that have not yet been introduced as routine clinical assays...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27907920/aneuploidy-detection-and-mtdna-quantification-in-bovine-embryos-with-different-cleavage-onset-using-a-next-generation-sequencing-based-protocol
#18
Miroslav Hornak, David Kubicek, Petr Broz, Pavlina Hulinska, Katerina Hanzalova, Darren Griffin, Marie Machatkova, Jiri Rubes
Bovine embryos are now routinely used in agricultural systems as a means of disseminating superior genetics worldwide, ultimately with the aim of feeding an ever-growing population. Further investigations, common for human IVF embryos, thus have priority to improve cattle IVF, as has screening for aneuploidy (abnormal chromosome number). Although the incidence and consequences of aneuploidy are well documented in human preimplantation embryos, they are less well known for the embryos of other animals. To address this, we assessed aneuploidy levels in thirty-one 2-cell bovine embryos derived from early- and late-cleaving zygotes...
December 2, 2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/27906631/mitochondrial-purine-and-pyrimidine-metabolism-and-beyond
#19
Liya Wang
Carefully balanced deoxynucleoside triphosphate (dNTP) pools are essential for both nuclear and mitochondrial genome replication and repair. Two synthetic pathways operate in cells to produce dNTPs, e.g., the de novo and the salvage pathways. The key regulatory enzymes for de novo synthesis are ribonucleotide reductase (RNR) and thymidylate synthase (TS), and this process is considered to be cytosolic. The salvage pathway operates both in the cytosol (TK1 and dCK) and the mitochondria (TK2 and dGK). Mitochondrial dNTP pools are separated from the cytosolic ones owing to the double membrane structure of the mitochondria, and are formed by the salvage enzymes TK2 and dGK together with NMPKs and NDPK in postmitotic tissues, while in proliferating cells the mitochondrial dNTPs are mainly imported from the cytosol produced by the cytosolic pathways...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906110/failed-upregulation-of-tfam-protein-and-mitochondrial-dna-in-oxidatively-deficient-fibers-of-chronic-obstructive-pulmonary-disease-locomotor-muscle
#20
Yana Konokhova, Sally Spendiff, R Thomas Jagoe, Sudhakar Aare, Sophia Kapchinsky, Norah J MacMillan, Paul Rozakis, Martin Picard, Mylène Aubertin-Leheudre, Charlotte H Pion, Jean Bourbeau, Russell T Hepple, Tanja Taivassalo
BACKGROUND: Low mitochondrial content and oxidative capacity are well-established features of locomotor muscle dysfunction, a prevalent and debilitating systemic occurrence in patients with chronic obstructive pulmonary disease (COPD). Although the exact cause is not firmly established, physical inactivity and oxidative stress are among the proposed underlying mechanisms. Here, we assess the impact of COPD pathophysiology on mitochondrial DNA (mtDNA) integrity, biogenesis, and cellular oxidative capacity in locomotor muscle of COPD patients and healthy controls...
February 18, 2016: Skeletal Muscle
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