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https://www.readbyqxmd.com/read/27873387/physical-exercise-remodels-visceral-adipose-tissue-and-mitochondrial-lipid-metabolism-in-rats-fed-a-high-fat-diet
#1
Sílvia Rocha-Rodrigues, Amaia Rodríguez, Sara Becerril, Beatriz Ramírez, I O Gonçalves, Jorge Beleza, Gema Frühbeck, António Ascensão, José Magalhães
We aimed to investigate the effects of two physical exercise models, voluntary physical activity (VPA) and endurance training (ET) as preventive and therapeutic strategies, respectively, on lipid accumulation regulators and mitochondrial content in VAT of rats fed a high-fat diet (HFD). Sprague Dawley rats (6 wks old, n=60) were assigned into sedentary and VPA groups fed isoenergetic diets: standard (S, 35 kcal% fat) or HFD (71 kcal% fat). The VPA groups had free access to wheel running during the entire protocol...
November 22, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27871875/pyruvate-dehydrogenase-has-a-major-role-in-mast-cell-function-and-its-activity-is-regulated-by-mitochondrial-mitf
#2
Israa Sharkia, Tal Hadad Erlich, Nadine Landolina, Miri Assayag, Alex Motzik, Inbal Rachmin, Gillian Kay, Ziv Porat, Sagi Tshori, Neville Berkman, Francesca Levi-Schaffer, Ehud Razin
BACKGROUND: We have recently observed that OXPHOS mediated ATP production is essential for mast cell function. Pyruvate dehydrogenase (PDH) is the main regulator of the Krebs cycle and is located upstream to the electron transport chain. However, the role of PDH in mast cell function has not been described. Microphthalmia transcription factor (MITF) regulates the development, number and function of mast cells. The localization of MITF to the mitochondria and its interaction with mitochondrial proteins has not been explored...
November 18, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27863025/decision-to-grow-or-to-invade-is-at-the-flick-of-metabolic-switch-pgc1%C3%AE
#3
Kristen S Hill, Minjung Kim
Cancer cells constantly reprogram their metabolism to meet anabolic and catabolic demands in real time. Increased aerobic glycolysis (the Warburg effect) is associated with highly proliferative tumors, since it confers several advantages to proliferating tumor cells by providing rapid ATP production from glycolysis and macromolecules (building blocks) for cell division. On the other hand, mitochondria-dependent oxidative phosphorylation (OxPhos) generates the maximal amount of ATP from glucose. Although underappreciated, OxPhos is also utilized to support growth of cancer cells, especially for "oxidative tumors" such as lymphomas, glioblastomas, and melanomas...
November 10, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27861795/sex-specific-mitonuclear-epistasis-and-the-evolution-of-mitochondrial-bioenergetics-ageing-and-life-history-in-seed-beetles
#4
Mirko Đorđević, Biljana Stojković, Uroš Savković, Elina Immonen, Nikola Tucić, Jelica Lazarević, Göran Arnqvist
The role of mitochondrial DNA for the evolution of life-history traits remains debated. We examined mitonuclear effects on the activity of the multisubunit complex of the electron transport chain (ETC) involved in oxidative phosphorylation (OXPHOS) across lines of the seed beetle Acanthoscelides obtectus selected for a short (E) or a long (L) life for more than >160 generations. We constructed and phenotyped mitonuclear introgression lines, which allowed us to assess the independent effects of the evolutionary history of the nuclear and the mitochondrial genome...
November 9, 2016: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/27861144/inhibition-of-oxidative-phosphorylation-suppresses-the-development-of-osimertinib-resistance-in-a-preclinical-model-of-egfr-driven-lung-adenocarcinoma
#5
Matthew J Martin, Cath Eberlein, Molly Taylor, Susan Ashton, David Robinson, Darren Cross
Metabolic plasticity is an emerging hallmark of cancer, and increased glycolysis is often observed in transformed cells. Small molecule inhibitors that target driver oncogenes can potentially inhibit the glycolytic pathway. Osimertinib (AZD9291) is a novel EGFR tyrosine kinase inhibitor (TKI) that is potent and selective for sensitising (EGFRm) and T790M resistance mutations. Clinical studies have shown osimertinib to be efficacious in patients with EGFRm/ T790M advanced NSCLC who have progressed after EGFR-TKI treatment...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27856430/glycolysis-and-oxidative-phosphorylation-are-essential-for-purinergic-receptor-mediated-angiogenic-responses-in-vasa-vasorum-endothelial-cells
#6
Martin Lapel, Philip Weston, Derek Strassheim, Vijaya Karoor, Nana Burns, Taras Lyubchenko, Petr Paucek, Kurt R Stenmark, Evgenia V Gerasimovskaya
Angiogenesis is an energy demanding process, however, the role of cellular energy pathways and their regulation by extracellular stimuli, especially extracellular nucleotides, remain largely unexplored. Using metabolic inhibitors of glycolysis (2-deoxyglucose, 2-DG) and oxidative phosphorylation (oligomycin, rotenone, and FCCP) we demonstrate that glycolysis and OXPHOS are both essential for angiogenic responses of vasa vasorum endothelial cell (VVEC). Treatment with P2R agonists, ATP and MeSADP, but not P1 receptor agonist, adenosine, increased glycolytic activity in VVEC (measured by extracellular acidification rate and lactate production)...
November 16, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27854030/simple-oxygraphic-analysis-for-the-presence-of-adenylate-kinase-1-and-2-in-normal-and-tumor-cells
#7
Aleksandr Klepinin, Lyudmila Ounpuu, Rita Guzun, Vladimir Chekulayev, Natalja Timohhina, Kersti Tepp, Igor Shevchuk, Uwe Schlattner, Tuuli Kaambre
The adenylate kinase (AK) isoforms network plays an important role in the intracellular energy transfer processes, the maintenance of energy homeostasis, and it is a major player in AMP metabolic signaling circuits in some highly-differentiated cells. For this purpose, a rapid and sensitive method was developed that enables to estimate directly and semi-quantitatively the distribution between cytosolic AK1 and mitochondrial AK2 localized in the intermembrane space, both in isolated cells and tissue samples (biopsy material)...
November 17, 2016: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/27826120/mitochondrial-oxidative-phosphorylation-disorders-in-children-phenotypic-genotypic-and-biochemical-correlations-in-85-patients-from-south-india
#8
Kothari Sonam, Parayil Sankaran Bindu, Mm Srinivas Bharath, Periyasamy Govindaraj, Narayanappa Gayathri, Hanumanthapura R Arvinda, Shwetha Chiplunkar, Madhu Nagappa, Sanjib Sinha, Nahid Akhtar Khan, Vandana Nunia, Arumugam Paramasivam, Kumarasamy Thangaraj, Arun B Taly
Mitochondrial oxidative phosphorylation (OXPHOS) disorders accounts for a variety of neuromuscular disorders in children. In this study mitochondrial respiratory chain enzymes were assayed in muscle tissue in a large cohort of children with varied neuromuscular presentations from June 2011 to December 2013. The biochemical enzyme deficiencies were correlated with the phenotypes, magnetic resonance imaging, histopathology and genetic findings to reach a final diagnosis. There were 85 children (mean age: 6.9±4...
November 5, 2016: Mitochondrion
https://www.readbyqxmd.com/read/27821095/treatment-of-a-chemoresistant-neuroblastoma-cell-line-with-the-antimalarial-ozonide-oz513
#9
Don W Coulter, Timothy R McGuire, John G Sharp, Erin M McIntyre, Yuxiang Dong, Xiaofang Wang, Shawn Gray, Gracey R Alexander, Nagendra K Chatuverdi, Shantaram S Joshi, Xiaoyu Chen, Jonathan L Vennerstrom
BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c. METHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing's Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments...
November 8, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27814641/the-little-big-genome-the-organization-of-mitochondrial-dna
#10
Iraselia Garcia, Edith Jones, Manuel Ramos, Wendy Innis-Whitehouse, Robert Gilkerson
The small (16,569 base pair) human mitochondrial genome plays a significant role in cell metabolism and homeostasis. Mitochondrial DNA (mtDNA) contributes to the generation of complexes which are essential to oxidative phosphorylation (OXPHOS). As such, mtDNA is directly integrated into mitochondrial biogenesis and signaling and regulates mitochondrial metabolism in concert with nuclear-encoded mitochondrial factors. Mitochondria are a highly dynamic, pleiomorphic network that undergoes fission and fusion events...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27812541/muscle-oxidative-phosphorylation-quantitation-using-creatine-chemical-exchange-saturation-transfer-crcest-mri-in-mitochondrial-disorders
#11
Catherine DeBrosse, Ravi Prakash Reddy Nanga, Neil Wilson, Kevin D'Aquilla, Mark Elliott, Hari Hariharan, Felicia Yan, Kristin Wade, Sara Nguyen, Diana Worsley, Chevonne Parris-Skeete, Elizabeth McCormick, Rui Xiao, Zuela Zolkipli Cunningham, Lauren Fishbein, Katherine L Nathanson, David R Lynch, Virginia A Stallings, Marc Yudkoff, Marni J Falk, Ravinder Reddy, Shana E McCormack
Systemic mitochondrial energy deficiency is implicated in the pathophysiology of many age-related human diseases. Currently available tools to estimate mitochondrial oxidative phosphorylation (OXPHOS) capacity in skeletal muscle in vivo lack high anatomic resolution. Muscle groups vary with respect to their contractile and metabolic properties. Therefore, muscle group-specific estimates of OXPHOS would be advantageous. To address this need, a noninvasive creatine chemical exchange saturation transfer (CrCEST) MRI technique has recently been developed, which provides a measure of free creatine...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27800515/phosphorylation-of-the-pyruvate-dehydrogenase-complex-precedes-hif-1-mediated-effects-and-pyruvate-dehydrogenase-kinase-1-upregulation-during-the-first-hours-of-hypoxic-treatment-in-hepatocellular-carcinoma-cells
#12
Andreas David Zimmer, Geoffroy Walbrecq, Ines Kozar, Iris Behrmann, Claude Haan
The pyruvate dehydrogenase complex (PDC) is an important gatekeeper enzyme connecting glycolysis to the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). Thereby, it has a strong impact on the glycolytic flux as well as the metabolic phenotype of a cell. PDC activity is regulated via reversible phosphorylation of three serine residues on the pyruvate dehydrogenase (PDH) E1α subunit. Phosphorylation of any of these residues by the PDH kinases (PDKs) leads to a strong decrease in PDC activity...
2016: Hypoxia
https://www.readbyqxmd.com/read/27793643/nuclear-but-not-mitochondrial-encoded-oxphos-genes-are-altered-in-aging-mild-cognitive-impairment-and-alzheimer-s-disease
#13
Diego Mastroeni, Omar M Khdour, Elaine Delvaux, Jennifer Nolz, Gary Olsen, Nicole Berchtold, Carl Cotman, Sidney M Hecht, Paul D Coleman
INTRODUCTION: We have comprehensively described the expression profiles of mitochondrial DNA and nuclear DNA genes that encode subunits of the respiratory oxidative phosphorylation (OXPHOS) complexes (I-V) in the hippocampus from young controls, age matched, mild cognitively impaired (MCI), and Alzheimer's disease (AD) subjects. METHODS: Hippocampal tissues from 44 non-AD controls (NC), 10 amnestic MCI, and 18 AD cases were analyzed on Affymetrix Hg-U133 plus 2...
October 25, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27780865/natural-and-induced-mitochondrial-phosphate-carrier-loss-differential-dependence-of-mitochondrial-metabolism-and-dynamics-and-cell-survival-on-the-extent-of-depletion
#14
Erin L Seifert, Aniko Gál, Michelle G Acoba, Qipei Li, Lauren Anderson-Pullinger, Tunde Golenár, Cynthia Moffat, Neal Sondheimer, Steven M Claypool, György Hajnóczky
The relevance of PiC, encoded by SLC25A3, in bioenergetics is well accepted. However, little is known about the mechanisms mediating the cellular impairments induced by pathological SLC25A3 variants. To this end, we investigated the pathogenicity of a novel compound heterozygous mutation in SLC25A3. First, each variant was modeled in yeast, revealing that substituting GSSAS for QIP within the 5th matrix loop is incompatible with survival on non-fermentable substrate whereas the L200W variant is functionally neutral...
October 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27778302/spotlight-on-the-relevance-of-mtdna-in-cancer
#15
A Cruz-Bermúdez, R J Vicente-Blanco, E Gonzalez-Vioque, M Provencio, M Á Fernández-Moreno, R Garesse
The potential role of the mitochondrial genome has recently attracted interest because of its high mutation frequency in tumors. Different aspects of mtDNA make it relevant for cancer's biology, such as it encodes a limited but essential number of genes for OXPHOS biogenesis, it is particularly susceptible to mutations, and its copy number can vary. Moreover, most ROS in mitochondria are produced by the electron transport chain. These characteristics place the mtDNA in the center of multiple signaling pathways, known as mitochondrial retrograde signaling, which modifies numerous key processes in cancer...
October 24, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27776434/codon-usage-bias-and-phylogenetic-analysis-of-mitochondrial-nd1-gene-in-pisces-aves-and-mammals
#16
Arif Uddin, Monisha Nath Choudhury, Supriyo Chakraborty
The mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) gene is a subunit of the respiratory chain complex I and involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). To understand the pattern of compositional properties, codon usage and expression level of mitochondrial ND1 genes in pisces, aves, and mammals, we used bioinformatic approaches as no work was reported earlier. In this study, a perl script was used for calculating nucleotide contents and different codon usage bias parameters...
October 24, 2016: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/27769573/relationships-between-mitochondrial-dna-content-mitochondrial-activity-and-boar-sperm-motility
#17
Huiduo Guo, Yabin Gong, Bin He, Ruqian Zhao
Energy produced by mitochondria via oxidative phosphorylation (OXPHOS) is essential for mammalian sperm motility. Mammalian mitochondrial DNA (mtDNA)-encoded proteins are subunits of the OXPHOS system. Paradoxically, there are less mitochondrial and mtDNA contents in motile sperm than less motile sperm. Here, mature boar sperm was used as a model to investigate the relationships between mtDNA content, mitochondrial activity, and sperm motility. Motile and less motile sperm were separated by centrifugation on a discontinuous percoll density gradient...
September 13, 2016: Theriogenology
https://www.readbyqxmd.com/read/27769281/novel-homozygous-rars2-mutation-in-two-siblings-without-pontocerebellar-hypoplasia-further-expansion-of-the-phenotypic-spectrum
#18
S Lühl, H Bode, W Schlötzer, M Bartsakoulia, R Horvath, A Abicht, M Stenzel, J Kirschner, S C Grünert
BACKGROUND: Pontocerebellar hypoplasia type 6 (PCH6) is a mitochondrial disease caused by mutations in the RARS2 gene. RARS2 encodes mitochondrial arginyl transfer RNA synthetase, an enzyme involved in mitochondrial protein translation. A total of 27 patients from 14 families have been reported so far. Characteristic clinical features comprise neonatal lactic acidosis, severe encephalopathy, intractable seizures, feeding problems and profound developmental delay. Most patients show typical neuroradiologic abnormalities including cerebellar hypoplasia and progressive pontocerebellar atrophy...
October 21, 2016: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/27768122/differential-contribution-of-the-mitochondrial-translation-pathway-to-the-survival-of-diffuse-large-b-cell-lymphoma-subsets
#19
Erik Norberg, Ana Lako, Pei-Hsuan Chen, Illana A Stanley, Feng Zhou, Scott B Ficarro, Bjoern Chapuy, Linfeng Chen, Scott Rodig, Donghyuk Shin, Dong Wook Choi, Sangho Lee, Margaret A Shipp, Jarrod A Marto, Nika N Danial
Diffuse large B-cell lymphomas (DLBCLs) are a highly heterogeneous group of tumors in which subsets share molecular features revealed by gene expression profiles and metabolic fingerprints. While B-cell receptor (BCR)-dependent DLBCLs are glycolytic, OxPhos-DLBCLs rely on mitochondrial energy transduction and nutrient utilization pathways that provide pro-survival benefits independent of BCR signaling. Integral to these metabolic distinctions is elevated mitochondrial electron transport chain (ETC) activity in OxPhos-DLBCLs compared with BCR-DLBCLs, which is linked to greater protein abundance of ETC components...
October 21, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27759031/whole-exome-sequencing-identifies-novel-variants-in-pnpt1-causing-oxidative-phosphorylation-defects-and-severe-multisystem-disease
#20
Ahmad Alodaib, Nara Sobreira, Wendy A Gold, Lisa G Riley, Nicole J Van Bergen, Meredith J Wilson, Bruce Bennetts, David R Thorburn, Corinne Boehm, John Christodoulou
Recent advances in next-generation sequencing strategies have led to the discovery of many novel disease genes. We describe here a non-consanguineous family with two affected boys presenting with early onset of severe axonal neuropathy, optic atrophy, intellectual disability, auditory neuropathy and chronic respiratory and gut disturbances. Whole-exome sequencing (WES) was performed on all family members and we identified compound heterozygous variants (c.[760C>A];[1528G>C];p.[(Gln254Lys);(Ala510Pro)] in the polyribonucleotide nucleotidyltransferase 1 (PNPT1) gene in both affected individuals...
October 19, 2016: European Journal of Human Genetics: EJHG
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