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Mitochondria DNA

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https://www.readbyqxmd.com/read/28208064/mitochondrial-genes-are-altered-in-blood-early-in-alzheimer-s-disease
#1
Katie Lunnon, Aoife Keohane, Ruth Pidsley, Stephen Newhouse, Joanna Riddoch-Contreras, Elisabeth B Thubron, Matthew Devall, Hikka Soininen, Iwona Kłoszewska, Patrizia Mecocci, Magda Tsolaki, Bruno Vellas, Leonard Schalkwyk, Richard Dobson, Afshan N Malik, John Powell, Simon Lovestone, Angela Hodges
Although mitochondrial dysfunction is a consistent feature of Alzheimer's disease in the brain and blood, the molecular mechanisms behind these phenomena are unknown. Here we have replicated our previous findings demonstrating reduced expression of nuclear-encoded oxidative phosphorylation (OXPHOS) subunits and subunits required for the translation of mitochondrial-encoded OXPHOS genes in blood from people with Alzheimer's disease and mild cognitive impairment. Interestingly this was accompanied by increased expression of some mitochondrial-encoded OXPHOS genes, namely those residing closest to the transcription start site of the polycistronic heavy chain mitochondrial transcript (MT-ND1, MT-ND2, MT-ATP6, MT-CO1, MT-CO2, MT-C03) and MT-ND6 transcribed from the light chain...
January 7, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28206987/id2-promotes-survival-of-glioblastoma-cells-during-metabolic-stress-by-regulating-mitochondrial-function
#2
Zhonghua Zhang, Gilbert J Rahme, Pranam D Chatterjee, Matthew C Havrda, Mark A Israel
Tumor cells proliferate in cellular environments characterized by a lack of optimal tissue organization resulting oftentimes in compromised cellular metabolism affecting nutrition, respiration, and energetics. The response of tumor cells to adverse environmental conditions is a key feature affecting their pathogenicity. We found that inhibitor of DNA binding 2 (ID2) expression levels significantly correlate with the ability of glioblastoma (GBM)-derived cell lines to survive glucose deprivation. ID2 suppressed mitochondrial oxidative respiration and mitochondrial ATP production by regulating the function of mitochondrial electron transport chain (mETC) complexes, resulting in reduced superoxide and reactive oxygen species (ROS) production from mitochondria...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28199200/mitochondrial-dna-mitochondrial-dysfunction-and-cardiac-manifestations
#3
Sung Ryul Lee, Nari Kim, Yeun Hee Noh, Zhelong Xu, Kyung Soo Ko, Byoung Doo Rhee, Jin Han
Mitochondria, are the powerhouses of cells, have their own DNA (mtDNA), regulate the transport of metabolites and ions, and impact cell physiology, survival, and death. Mitochondrial dysfunction, including impaired oxidative phosphorylation, preferentially affects heart function due to an imbalance of energy supply and demand. Recently, mitochondrial mutations and associated mitochondrial dysfunction were suggested as a causal factor of cardiac manifestations. Oxidative stress largely influences mtDNA stability due to oxidative modifications of mtDNA...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28199112/mitochondrial-gene-therapy-advances-in-mitochondrial-gene-cloning-plasmid-production-and-nanosystems-targeted-to-mitochondria
#4
Eduarda Coutinho, Cátia Batista, Fani Sousa, João Queiroz, Diana Costa
Mitochondrial gene therapy seems to be a valuable and promising strategy to treat mitochondrial disorders. The use of a therapeutic vector based on mitochondrial DNA, along with its affinity to the site of mitochondria can be considered a powerful tool in the reestablishment of normal mitochondrial function. In line with this and for the first time, we successfully cloned the mitochondrial gene ND1 that was stably maintained in multi-copy pCAG-GFP plasmid, used to transform E. coli. This mitochondrial gene based plasmid was encapsulated into nanoparticles...
February 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28197625/different-effect-of-resveratrol-to-induction-of-apoptosis-depending-on-the-type-of-human-cancer-cells
#5
Michinori Takashina, Sayaka Inoue, Kei Tomihara, Kengo Tomita, Kohshi Hattori, Qing-Li Zhao, Tokiko Suzuki, Makoto Noguchi, Wakana Ohashi, Yuichi Hattori
The effect of resveratrol on various human cancer cells was investigated with special focus on apoptotic cell death, in an attempt to further characterize its mechanism of action. There were great differences in the anti-viability effect of resveratrol between different types of human cancer cells. While the inhibition of cell viability by resveratrol was marked in U937 and MOLT-4 leukemia cells, resveratrol moderately inhibited cell viability in MCF-7 breast, HepG2 liver, and A549 lung cancer cells, and the effect was slight on cell viability in Caco-2, HCT116, and SW480 colon cancer cells...
January 24, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28195557/biogenetic-and-morphofunctional-heterogeneity-of-mitochondria-the-case-of-synaptic-mitochondria
#6
Sergei V Fedorovich, Tatyana V Waseem, Ludmila V Puchkova
The mitochondria of different cells are different in their morphological and biochemical properties. These organelles generate free radicals during activity, leading inevitably to mitochondrial DNA damage. It is not clear how this problem is addressed in long-lived cells, such as neurons. We propose the hypothesis that mitochondria within the same cell also differ in lifespan and ability to divide. According to our suggestion, cells have a pool of 'stem' mitochondria with low metabolic activity and a pool of 'differentiated' mitochondria with significantly shorter lifespans and high metabolic activity...
February 14, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28195532/horizontal-transfer-of-whole-mitochondria-restores-tumorigenic-potential-in-mitochondrial-dna-deficient-cancer-cells
#7
Lan-Feng Dong, Jaromira Kovarova, Martina Bajzikova, Ayenachew Bezawork-Geleta, David Svec, Berwini Endaya, Karishma Sachaphibulkij, Ana R Coelho, Natasa Sebkova, Anna Ruzickova, An S Tan, Katarina Kluckova, Kristyna Judasova, Katerina Zamecnikova, Zuzana Rychtarcikova, Vinod Gopalan, Margaryta Sobol, Bing Yan, Bijay Pattnaik, Naveen Bhatraju, Jaroslav Truksa, Pavel Stopka, Pavel Hozak, Alfred Lam, Radislav Sedlacek, Paulo J Oliveira, Mikael Kubista, Anurag Agrawal, Katerina Dvorakova-Hortova, Jakub Rohlena, Michael V Berridge, Jiri Neuzil
Recently we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (ρ(0) cells) is linked to acquisition of the host mtDNA. However, the mechanism of mtDNA movement between cells remains unresolved. To determine whether transfer of mtDNA involves whole mitochondria, we injected B16ρ(0) mouse melanoma cells into syngeneic C57BL/6N(su9-DsRed2) mice that express red fluorescent protein in their mitochondria. We document that mtDNA is acquired by transfer of whole mitochondria from the host animal, leading to normalisation of mitochondrial respiration...
February 14, 2017: ELife
https://www.readbyqxmd.com/read/28194828/mitochondrial-dysfunction-and-ovarian-aging
#8
Tianren Wang, Man Zhang, Zongliang Jiang, Emre Seli
Mitochondria are double-membrane-bound organelles that are responsible for the generation of most of the cell's energy. Mitochondrial dysfunction has been implicated in cellular senescence in general and ovarian aging in particular. Recent studies exploited this association by studying mitochondrial DNA (mtDNA) copy number as a potential biomarker of embryo viability and the use of mitochondrial nutrients and autologous mitochondrial transfer as a potential treatment for poor ovarian function and response.
February 13, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28193734/mitochondrial-depolarization-in-yeast-zygotes-inhibits-clonal-expansion-of-selfish-mtdna
#9
Iuliia E Karavaeva, Sergey A Golyshev, Ekaterina A Smirnova, Svyatoslav S Sokolov, Fedor F Severin, Dmitry A Knorre
Non-identical copies of mitochondrial DNA (mtDNA) compete with each other within a cell and the result depends on their replication rates. Using yeast Saccharomyces cerevisiae cells as a model, we studied the effects of mitochondrial inhibitors on the competition between wild type mtDNA and mutant selfish mtDNA in heteroplasmic zygotes. We found that decreasing mitochondrial transmembrane potential by adding uncouplers or valinomycin changes the competition outcomes in favor of the wild type mtDNA. This effect was significantly lower in the cells with disrupted mitochondria fission or repressed autophagy-related genes ATG8, ATG32 or ATG33 implying that heteroplasmic zygotes activate mitochondrial degradation in response to the depolarization...
February 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28193566/in-vitro-evaluation-of-ruthenium-complexes-for-photodynamic-therapy
#10
Wenna Li, Qiang Xie, Linglin Lai, Zhentao Mo, Xiaofang Peng, Ennian Leng, Dandan Zhang, Hongxia Sun, Yiqi Li, Wenjie Mei, Shuying Gao
BACKGROUND: Photodynamic therapy (PDT) is a promising new anti-tumor treatment strategy. Photosensitizer is one of the most important components of PDT. In this work, the anticancer activities of PDTs mediated by six new ruthenium porphyrin complexes were screened. The mechanisms of the most efficacious candidate were investigated. METHODS: Photocytotoxicity of the six porphyrins was tested. The most promising complex, Rup-03, was further investigated using Geimsa staining, which indirectly detects reactive oxygen species (ROS) and subcellular localization...
February 10, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28189066/mdh2-stimulated-by-estrogen-gpr30-pathway-down-regulated-pten-expression-promoting-the-proliferation-and-invasion-of-cells-in-endometrial-cancer
#11
Yan Zhuang, Jiangdong Xiang, Wei Bao, Ya Sun, Lina Wang, Meihua Tan, Yinyan He, Xiaowei Xi
PURPOSE: The relationship between endometrial carcinoma and cellular metabolism is unknown. In endometrial cancer, mutation rate of PTEN has been reported very high. Malate dehydrogenase 2 (MDH2) is one of the isoforms of malate dehydrogenase, which is involved in citric acid cycle in mitochondria. Our study aimed to investigate the role MDH2 played in PTEN-regulated endometrial carcinoma. METHODS: To reveal the expression of MDH2 and the co-localization of PTEN and MDH2, immunohistochemistry and immunofluorescent staining were used...
February 8, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28188263/overexpression-of-mitochondrial-oxodicarboxylate-carrier-odc1-preserves-oxidative-phosphorylation-in-a-yeast-model-of-the-barth-syndrome
#12
Maxence de Taffin de Tilques, Déborah Tribouillard-Tanvier, Emmanuel Tétaud, Eric Testet, Jean-Paul di Rago, Jean-Paul Lasserre
Cardiolipin (CL) is a diglycerol phospholipid mostly found in mitochondria where it optimizes numerous processes including oxidative phosphorylation (OXPHOS). To function properly CL needs to be unsaturated, which requires the acyltransferase tafazzin. Loss-of-function mutations in this protein are responsible for the Barth syndrome (BTHS), presumably because of a diminished OXPHOS capacity. Here we show that overexpressing Odc1p, a conserved oxodicarboxylic acid carrier located in the mitochondrial inner membrane, fully restores oxidative phosphorylation in a yeast model (taz1Δ) of the Barth syndrome...
February 10, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28186130/identification-of-symmetrical-rna-editing-events-in-the-mitochondria-of-salvia-miltiorrhiza-by-strand-specific-rna-sequencing
#13
Bin Wu, Haimei Chen, Junjie Shao, Hui Zhang, Kai Wu, Chang Liu
Salvia miltiorrhiza is one of the most widely-used medicinal plants. Here, we systematically analyzed the RNA editing events in its mitochondria. We developed a pipeline using REDItools to predict RNA editing events from stand-specific RNA-Seq data. The predictions were validated using reverse transcription, RT-PCR amplification and Sanger sequencing experiments. Putative sequences motifs were characterized. Comparative analyses were carried out between S. miltiorrhiza, Arabidopsis thaliana and Oryza sativa...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28185435/evidence-that-a-mitochondrial-death-spiral-underlies-antagonistic-pleiotropy
#14
REVIEW
Michael Stern
The antagonistic pleiotropy (AP) theory posits that aging occurs because alleles that are detrimental in older organisms are beneficial to growth early in life and thus are maintained in populations. Although genes of the insulin signaling pathway likely participate in AP, the insulin-regulated cellular correlates of AP have not been identified. The mitochondrial quality control process called mitochondrial autophagy (mitophagy), which is inhibited by insulin signaling, might represent a cellular correlate of AP...
February 9, 2017: Aging Cell
https://www.readbyqxmd.com/read/28183804/reduced-mitochondrial-activity-in-colonocytes-facilitates-ampk%C3%AE-2-dependent-inflammation
#15
Sandra Heller, Harrison M Penrose, Chloe Cable, Debjani Biswas, Hani Nakhoul, Melody Baddoo, Erik Flemington, Susan E Crawford, Suzana D Savkovic
Intestinal inflammation is associated with low levels of mucosal ATP, highlighting the importance of mitochondrial function associated with ATP production in the pathophysiology of the disease. In the inflamed colon of humans and mice, we found decreased levels of mitochondrial complex cytochrome c oxidase I/IV and lower ATP levels. Thus, we generated colonic ρ(0) cells with reduced mitochondrial function linked to ATP production by selective depletion of mitochondrial DNA. In these cells, RNA sequencing revealed a substantial number of differentially expressed transcripts, among which 240 belonged to inflammatory pathways activated in human inflamed colon and TNF-α-treated cells (false discovery rate < 0...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28181523/mitochondria-play-an-important-role-in-the-cell-proliferation-suppressing-activity-of-berberine
#16
Xiao-Jin Yan, Xuan Yu, Xin-Pei Wang, Jing-Fei Jiang, Zhi-Yi Yuan, Xi Lu, Fan Lei, Dong-Ming Xing
After being studied for approximately a century, berberine (BBR) has been found to act on various targets and pathways. A great challenge in the pharmacological analysis of BBR at present is to identify which target(s) plays a decisive role. In the study described herein, a rescue experiment was designed to show the important role of mitochondria in BBR activity. A toxic dose of BBR was applied to inhibit cell proliferation and mitochondrial activity, then α-ketobutyrate (AKB), an analogue of pyruvate that serves only as an electron receptor of NADH, was proven to partially restore cell proliferation...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181380/fisetin-induced-apoptosis-of-human-oral-cancer-scc-4-cells-through-reactive-oxygen-species-production-endoplasmic-reticulum-stress-caspase-and-mitochondria-dependent-signaling-pathways
#17
Chen-Hsuan Su, Chao-Lin Kuo, Kung-Wen Lu, Fu-Shun Yu, Yi-Shih Ma, Jiun-Long Yang, Yung-Lin Chu, Fu-Shin Chueh, Kuo-Ching Liu, Jing-Gung Chung
Oral cancer is one of the cancer-related diseases in human populations and its incidence rates are rising worldwide. Fisetin, a flavonoid from natural products, has been shown to exhibit anticancer activities in many human cancer cell lines but the molecular mechanism of fisetin-induced apoptosis in human oral cancer cells is still unclear; thus, in this study, we investigated fisetin-induced cell death and associated signal pathways on human oral cancer SCC-4 cells in vitro. We examined cell morphological changes, total viable cells, and cell cycle distribution by phase contrast microscopy and flow cytometry assays...
February 9, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28179510/when-coi-barcodes-deceive-complete-genomes-reveal-introgression-in-hairstreaks
#18
Qian Cong, Jinhui Shen, Dominika Borek, Robert K Robbins, Paul A Opler, Zbyszek Otwinowski, Nick V Grishin
Two species of hairstreak butterflies from the genus Calycopis are known in the United States: C. cecrops and C. isobeon Analysis of mitochondrial COI barcodes of Calycopis revealed cecrops-like specimens from the eastern US with atypical barcodes that were 2.6% different from either USA species, but similar to Central American Calycopis species. To address the possibility that the specimens with atypical barcodes represent an undescribed cryptic species, we sequenced complete genomes of 27 Calycopis specimens of four species: C...
February 8, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28178941/implications-of-human-evolution-and-admixture-for-mitochondrial-replacement-therapy
#19
Lavanya Rishishwar, I King Jordan
BACKGROUND: Mitochondrial replacement (MR) therapy is a new assisted reproductive technology that allows women with mitochondrial disorders to give birth to healthy children by combining their nuclei with mitochondria from unaffected egg donors. Evolutionary biologists have raised concerns about the safety of MR therapy based on the extent to which nuclear and mitochondrial genomes are observed to co-evolve within natural populations, i.e. the nuclear-mitochondrial mismatch hypothesis...
February 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28178347/mitochondria-penetrating-peptides-conjugated-to-desferrioxamine-as-chelators-for-mitochondrial-labile-iron
#20
Roxana Y P Alta, Hector A Vitorino, Dibakar Goswami, Cleber W Liria, Simon P Wisnovsky, Shana O Kelley, M Terêsa Machini, Breno P Espósito
Desferrioxamine (DFO) is a bacterial siderophore with a high affinity for iron, but low cell penetration. As part of our ongoing project focused on DFO-conjugates, we synthesized, purified, characterized and studied new mtDFOs (DFO conjugated to the Mitochondria Penetrating Peptides TAT49-57, 1A, SS02 and SS20) using a succinic linker. These new conjugates retained their strong iron binding ability and antioxidant capacity. They were relatively non toxic to A2780 cells (IC50 40-100 μM) and had good mitochondrial localization (Rr +0...
2017: PloS One
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