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https://www.readbyqxmd.com/read/28225235/-multiple-sclerosis-a-mitochondria-mediated-disease
#1
Kristin N Varhaug, Christian A Vedeler, Charalampos Tzoulis, Laurence A Bindoff
BACKGROUND Mitochondria play an important role in the pathogenesis of various neurodegenerative disorders, including Parkinson's disease. Neurodegenerative changes occur early in the course of multiple sclerosis (MS). This article aims to present information on a possible association between mitochondrial dysfunction and multiple sclerosis.MATERIAL AND METHOD The article is based on original and review articles selected following a literature search in PubMed, restricted to articles written in English, and concluded in May 2016...
February 2017: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
https://www.readbyqxmd.com/read/28224387/evaluation-of-the-ros-inhibiting-activity-and-mitochondrial-targeting-of-phenolic-compounds-in-fibroblast-cells-model-system-and-enhancement-of-efficiency-by-natural-deep-eutectic-solvent-nades-formulation
#2
Erwann Durand, Jérôme Lecomte, Rashmi Upasani, Béatrice Chabi, Christelle Bayrasy, Bruno Baréa, Elodie Jublanc, Martyn J Clarke, David J Moore, Jonathan Crowther, Chantal Wrutniak-Cabello, Pierre Villeneuve
PURPOSE: Many phenolics have already been tested for their antioxidant activities using in vitro methods. However, such assays do not consider the complexity of real cellular systems, and most of the phenolics characterized with such assays shows disappointing results when evaluated in cells. Accordingly, there is a need to develop effective screening methods. METHODS: Antioxidants were first evaluated by CAT assay and then, evaluated for their ability (i) to reduce the level of ROS using fluorescent probe, (ii) to cross fibroblast cell membranes using confocal microscopy, and (iii) to target mitochondria...
February 21, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28224174/spectroscopic-polarographic-and-microcalorimetric-studies-on-mitochondrial-dysfunction-induced-by-ethanol
#3
Long Ma, Jia-Xin Dong, Can Wu, Xue-Yi Li, Jing Chen, Hong Zhang, Yi Liu
Liver mitochondria are involved in several important life processes; mitochondrial dysfunction and disorders are implicated in several human diseases. Alcohol permeates all tissues of the body and exerts some intrinsic hepatotoxicity. In this work, our results demonstrated that ethanol caused a series of mitochondria permeability transition pore (MPTP) opening factors such as mitochondrial swelling, increased permeability of H(+) and K(+), collapsed membrane potential, and increased membrane fluidity. Furthermore, mitochondrial ultrastructure alternation observed clearly by transmission electron microscopy and the release of Cytochrome c could explain the MPTP opening from another aspect...
February 21, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28221768/formation-of-nitrogenase-nifdk-tetramers-in-the-mitochondria-of-saccharomyces-cerevisiae
#4
Stefan Burén, Eric M Young, Elizabeth A Sweeny, Gema López-Torrejón, Marcel Veldhuizen, Christopher A Voigt, Luis M Rubio
Transferring the prokaryotic enzyme nitrogenase into a eukaryotic host with the final aim of developing N2 fixing cereal crops would revolutionize agricultural systems worldwide. Targeting it to mitochondria has potential advantages because of the organelle's high O2 consumption and the presence of bacterial-type iron-sulfur cluster biosynthetic machinery. In this study, we constructed 96 strains of Saccharomyces cerevisiae where transcriptional units comprising nine Azotobacter vinelandii nif genes (nifHDKUSMBEN) were integrated into the genome...
February 21, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28217742/piericidin-a1-blocks-yersinia-ysc-type-iii-secretion-system-needle-assembly
#5
Jessica M Morgan, Miles C Duncan, Kevin S Johnson, Andreas Diepold, Hanh Lam, Allison J Dupzyk, Lexi R Martin, Weng Ruh Wong, Judith P Armitage, Roger G Linington, Victoria Auerbuch
The type III secretion system (T3SS) is a bacterial virulence factor expressed by dozens of Gram-negative pathogens but largely absent from commensals. The T3SS is an attractive target for antimicrobial agents that may disarm pathogenic bacteria while leaving commensal populations intact. We previously identified piericidin A1 as an inhibitor of the Ysc T3SS in Yersinia pseudotuberculosis. Piericidins were first discovered as inhibitors of complex I of the electron transport chain in mitochondria and some bacteria...
January 2017: MSphere
https://www.readbyqxmd.com/read/28217180/hypoxic-pulmonary-vasoconstriction-in-humans-tale-or-myth
#6
REVIEW
A Hussain, M S Suleiman, S J George, M Loubani, A Morice
Hypoxic Pulmonary vasoconstriction (HPV) describes the physiological adaptive process of lungs to preserves systemic oxygenation. It has clinical implications in the development of pulmonary hypertension which impacts on outcomes of patients undergoing cardiothoracic surgery. This review examines both acute and chronic hypoxic vasoconstriction focusing on the distinct clinical implications and highlights the role of calcium and mitochondria in acute versus the role of reactive oxygen species and Rho GTPases in chronic HPV...
2017: Open Cardiovascular Medicine Journal
https://www.readbyqxmd.com/read/28215509/triphenylphosphonium-modified-poly-ethylene-glycol-poly-%C3%AE%C2%B5-caprolactone-micelles-for-mitochondria-targeted-gambogic-acid-delivery
#7
Yingqi Xu, Shengpeng Wang, Hon Fai Chan, Yuling Liu, Hui Li, Chengwei He, Zeyong Li, Meiwan Chen
Mitochondria are important targets for the intracellular delivery of drugs and DNA. For mitochondria-targeted delivery, a mitochondriotropic molecule, triphenylphosphonium (TPP), was applied to the synthesis of amphiphilic TPP-poly(ethylene glycol)-poly(ε-caprolactone) (TPP-PEG-PCL) polymers. The TPP-PEG-PCL polymer was used to prepare micelles using a solvent evaporation method for the delivery of gambogic acid (GA) (GA-TPP). The micelles were obtained with a favorable particle size of 150.07±11.71nm and an encapsulation efficiency of 80...
February 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#8
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212735/elimination-of-the-unnecessary-intra-and-extracellular-signaling-by-anionic-phospholipids
#9
REVIEW
Valerian E Kagan, Hülya Bayır, Yulia Y Tyurina, Sergey B Bolevich, John J Maguire, Bengt Fadeel, Krishnakumar Balasubramanian
High fidelity of biological systems is frequently achieved by duplication of the essential intracellular machineries or, removal of the entire cell, which becomes unnecessary or even harmful in altered physiological environments. Carefully controlled removal of these cells, without damaging normal cells, requires precise signaling, and is critical to maintaining homeostasis. This review describes how two anionic phospholipids - phosphatidylserine (PS) and cardiolipin (CL) - residing in distinct compartments of the cell, signal removal of "the unnecessary" using several uniform principles...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28209717/autophagy-metabolism-and-cancer
#10
Jessie Yanxiang Guo, Eileen White
Macroautophagy (autophagy hereafter) is a process that collects cytoplasmic components, particularly mitochondria, and degrades them in lysosomes. In mammalian systems, basal autophagy levels are normally low but are profoundly stimulated by starvation and essential for survival. Cancer cells up-regulate autophagy and can be more autophagy-dependent than most normal tissues. Genetic deficiency in essential autophagy genes in tumors in many autochthonous mouse models for cancer reduces tumor growth. In K-ras(G12D)-driven non-small cell lung cancer (NSCLC) and other models, autophagy sustains metabolism and survival...
February 16, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28199200/mitochondrial-dna-mitochondrial-dysfunction-and-cardiac-manifestations
#11
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/28192238/molecular-networks-related-to-the-immune-system-and-mitochondria-are-targets-for-the-pesticide-dieldrin-in-the-zebrafish-danio-rerio-central-nervous-system
#12
Andrew M Cowie, Kathleena I Sarty, Angella Mercer, Jin Koh, Karen A Kidd, Christopher J Martyniuk
: The objectives of this study were to determine the behavioral and molecular responses in the adult zebrafish (Danio rerio) central nervous system (CNS) following a dietary exposure to the pesticide dieldrin. Zebrafish were fed pellets spiked with 0.03, 0.15, or 1.8μg/g dieldrin for 21days. Behavioral analysis revealed no difference in exploratory behaviors or those related to anxiety. Transcriptional networks for T-cell aggregation and selection were decreased in expression suggesting an immunosuppressive effect of dieldrin, consistent with other studies investigating organochlorine pesticides...
February 9, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28186127/optogenetic-control-of-cellular-forces-and-mechanotransduction
#13
Léo Valon, Ariadna Marín-Llauradó, Thomas Wyatt, Guillaume Charras, Xavier Trepat
Contractile forces are the end effectors of cell migration, division, morphogenesis, wound healing and cancer invasion. Here we report optogenetic tools to upregulate and downregulate such forces with high spatiotemporal accuracy. The technology relies on controlling the subcellular activation of RhoA using the CRY2/CIBN light-gated dimerizer system. We fused the catalytic domain (DHPH domain) of the RhoA activator ARHGEF11 to CRY2-mCherry (optoGEF-RhoA) and engineered its binding partner CIBN to bind either to the plasma membrane or to the mitochondrial membrane...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28183062/thioredoxin-trxo1-interacts-with-proliferating-cell-nuclear-antigen-pcna-and-its-overexpression-affects-the-growth-of-tobacco-cell-culture
#14
Aingeru Calderón, Ana Ortiz-Espín, Raquel Iglesias-Fernández, Pilar Carbonero, Federico Vicente Pallardó, Francisca Sevilla, Ana Jiménez
Thioredoxins (Trxs), key components of cellular redox regulation, act by controlling the redox status of many target proteins, and have been shown to play an essential role in cell survival and growth. The presence of a Trx system in the nucleus has received little attention in plants, and the nuclear targets of plant Trxs have not been conclusively identified. Thus, very little is known about the function of Trxs in this cellular compartment. Previously, we studied the intracellular localization of PsTrxo1 and confirmed its presence in mitochondria and, interestingly, in the nucleus under standard growth conditions...
January 31, 2017: Redox Biology
https://www.readbyqxmd.com/read/28181922/burn-serum-stimulates-myoblast-cell-death-associated-with-il-6-induced-mitochondrial-fragmentation
#15
Alvand Sehat, Ryan M Huebinger, Deborah L Carlson, Qun S Zang, Steven E Wolf, Juquan Song
BACKGROUND: Burn patients suffer muscle mass loss associated with hyperinflammation and hypercatabolism. The mitochondria are affected by this metabolic alteration. Mitochondrial fission activates a caspase cascade which ultimately leads to cell death. We postulate that burn-induced muscle loss is associated with increased mitochondrial fission and subsequent functional impairment. Further, we investigated whether the cytokine IL-6 plays a major role in mitochondrial fission-associated cell death after burn...
February 8, 2017: Shock
https://www.readbyqxmd.com/read/28177124/acute-exercise-elicits-differential-expression-of-insulin-resistance-genes-in-the-skeletal-muscle-of-patients-with-polycystic-ovary-syndrome
#16
Wagner Silva Dantas, Igor Hisashi Murai, Luiz Augusto Perandini, Hatylas Azevedo, Carlos Alberto Moreira-Filho, Niels Olsen Saraiva Camara, Hamilton Roschel, Bruno Gualano
OBJECTIVE: This study aimed to explore the role of acute exercise on skeletal muscle gene expression related to insulin resistance in patients with polycystic ovary syndrome (PCOS) and controls. METHODS: Four obese women with PCOS and 4 body controls subjects (CTRL) participated in this study. After an overnight fast, the subjects underwent a single 40-minute bout of aerobic exercise. Muscle samples were obtained from vastus lateralis at baseline and 60 minutes after exercise...
February 8, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28176017/hypoxia-and-aerobic-metabolism-adaptations-of-human-endothelial-cells
#17
Agnieszka Koziel, Wieslawa Jarmuszkiewicz
The goal of our study was to assess the influence of chronic exposure to hypoxia on mitochondrial oxidative metabolism in human umbilical vein endothelial cells (EA.hy926 line) cultured for 6 days at 1% O2 tension. The hypoxia-induced effects were elucidated at the cellular and isolated mitochondria levels. Hypoxia elevated fermentation but did not change mitochondrial biogenesis or the aerobic respiratory capacity of endothelial cells. In endothelial cells, hypoxia caused a general decrease in mitochondrial respiration during carbohydrate, fatty acid, and amino acid oxidation but increased exclusively ketogenic amino acid oxidation...
February 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28174301/respiratory-complex-i-in-bos-taurus-and-paracoccus-denitrificans-pumps-four-protons-across-the-membrane-for-every-nadh-oxidized
#18
Andrew J Y Jones, James N Blaza, Febin Varghese, Judy Hirst
Respiratory complex I couples electron transfer between NADH and ubiquinone to proton translocation across an energy-transducing membrane, to support the proton-motive force that drives ATP synthesis. The proton-pumping stoichiometry of complex I (i.e. the number of protons pumped for each two electrons transferred) underpins all mechanistic proposals. However, it remains controversial and has not been determined for any of the bacterial enzymes that are exploited as model systems for the mammalian enzyme. Here, we describe a simple method for determining the proton-pumping stoichiometry of complex I in inverted membrane vesicles under steady-state ADP-phosphorylating conditions...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28167700/the-transcription-factor-myb29-is-a-regulator-of-alternative-oxidase-1
#19
Xinhua Zhang, Aneta Ivanova, Klaas Vandepoele, Jordan D Radomiljac, Jan Van de Velde, Oliver Berkowitz, Patrick Willems, Yue Xu, Sophia Ng, Olivier Van Aken, Owen Duncan, Botao Zhang, Véronique Storme, Kai Xun Chan, Dries Vaneechoutte, Barry J Pogson, Frank Van Breusegem, James Whelan, Inge De Clercq
Plants sense and integrate a variety of signals from the environment through various interacting signal transduction pathways that involve hormones and signaling molecules. Using the ALTERNATIVE OXIDASE 1a (AOX1a) gene expression as a model system of retrograde or stress signaling between mitochondria and the nucleus, the MYB DOMAIN PROTEIN 29 (MYB29) was identified as a negative regulator (rao7 mutant) in a genetic screen of Arabidopsis thaliana. rao7/myb29 mutants have increased levels of AOX1a at a transcript and protein level after induction with antimycin A...
February 6, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28164076/systemic-primary-carnitine-deficiency-with-hypoglycemic-encephalopathy
#20
Jae Sung Jun, Eun Joo Lee, Hyung Doo Park, Hae Sook Kim
Acute hypoglycemia in children is not an uncommon disease that can be encountered in the Emergency Department. Most cases of childhood hypoglycemia are caused by ketotic hypoglycemia due to missed meals. Often, hypoketotic hypoglycemia can also occur, which suggests hyperinsulinemia or a defect in fatty acid oxidation. Carnitine is essential for long chain fatty acids transfer into mitochondria for oxidation. We present a case of systemic primary carnitine deficiency who presented with seizures due to hypoketotic hypoglycemia...
December 2016: Annals of Pediatric Endocrinology & Metabolism
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