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mitochondrial complex II

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https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#1
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28540186/novel-recessive-mutations-in-coq4-cause-severe-infantile-cardiomyopathy-and-encephalopathy-associated-with-coq10-deficiency
#2
Neal Sondheimer, Stacy Hewson, Jessie M Cameron, Gino R Somers, Jane Dunning Broadbent, Marcello Ziosi, Catarina Maria Quinzii, Ali B Naini
Coenzyme Q10 (CoQ10) or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ10 synthesis are usually associated with the impaired function of CoQ10-dependent complexes I, II and III. The recessively transmitted CoQ10 deficiency has been associated with a number of phenotypically and genetically heterogeneous groups of disorders manifesting at variable age of onset. The infantile, multisystemic presentation is usually caused by mutations in genes directly involved in CoQ10 biosynthesis...
September 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28537848/influence-of-endurance-training-on-skeletal-muscle-mitophagy-regulatory-proteins-in-type-2-diabetic-men
#3
Christian Brinkmann, Axel Przyklenk, Alexander Metten, Thorsten Schiffer, Wilhelm Bloch, Klara Brixius, Sebastian Gehlert
BACKGROUND: Mitophagy is a form of autophagy for the elimination of mitochondria. Mitochondrial content and function are reduced in the skeletal muscle of patients with type 2 diabetes mellitus (T2DM). Physical training has been shown to restore mitochondrial capacity in T2DM patients, but the role of mitophagy has not been examined in this context. This study analyzes the impact of a 3-month endurance training on important skeletal muscle mitophagy regulatory proteins and oxidative phosphorylation (OXPHOS) complexes in T2DM patients...
May 24, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28536862/mechanisms-of-hepatotoxicity-associated-with-the-monocyclic-%C3%AE-lactam-antibiotic-bal30072
#4
Franziska Paech, Simon Messner, Jochen Spickermann, Mathias Wind, Anne-Hortense Schmitt-Hoffmann, Anne Therese Witschi, Brett A Howell, Rachel J Church, Jeff Woodhead, Marc Engelhardt, Stephan Krähenbühl, Martina Maurer
BAL30072 is a new monocyclic β-lactam antibiotic under development which provides a therapeutic option for the treatment of severe infections caused by multi-drug-resistant Gram-negative bacteria. Despite the absence of liver toxicity in preclinical studies in rats and marmosets and in single dose clinical studies in humans, increased transaminase activities were observed in healthy subjects in multiple-dose clinical studies. We, therefore, initiated a comprehensive program to find out the mechanisms leading to hepatocellular injury using HepG2 cells (human hepatocellular carcinoma cell line), HepaRG cells (inducible hepatocytes derived from a human hepatic progenitor cell line), and human liver microtissue preparations...
May 23, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28526448/the-catechol-o-methyltransferase-inhibitors-tolcapone-and-entacapone-uncouple-and-inhibit-the-mitochondrial-respiratory-chain-in-heparg-cells
#5
David Grünig, Andrea Felser, Jamal Bouitbir, Stephan Krähenbühl
The catechol-O-methyltransferase inhibitor tolcapone causes hepatotoxicity and mitochondrial damage in animal models. We studied the interaction of tolcapone with mitochondrial respiration in comparison to entacapone in different experimental models. In HepaRG cells (human cell-line), tolcapone decreased the ATP content (estimated IC50 100±15μM) and was cytotoxic (estimated IC50 333±45μM), whereas entacapone caused no cytotoxicity and no ATP depletion up to 200μM. Cytochrome P450 induction did not increase the toxicity of the compounds...
May 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28525795/the-role-of-secretory-phospholipases-as-therapeutic-targets-for-the-treatment-of-myocardial-ischemia-reperfusion-injury
#6
REVIEW
Sriram Ravindran, Gino A Kurian
Myocardial reperfusion injury is a consequence of restoration of blood flow post ischemia. It is a complex process involving an acute inflammatory response activated by cytokines, chemokines, growth factors, and mediated by free radicals, calcium overload leading to mitochondrial dysfunction. Secretory phospholipases (sPLA2) are a group of pro-inflammatory molecules associated with diseases such as atherosclerosis, which increase the risk of reperfusion injury. This acute response leads to breakdown of phospholipids such as cardiolipin, found in the mitochondrial inner membrane, leading to disruption of energy producing enzymes of the electron transport chain...
May 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28523727/synthesis-and-antineoplastic-evaluation-of-mitochondrial-complex-ii-succinate-dehydrogenase-inhibitors-derived-from-atpenin-a5
#7
Hezhen Wang, Bader Huwaimel, Kshitij Verma, James Miller, Todd Germain, Nihar Kinarivala, Dimitri Pappas, Paul Brookes, Paul Charles Trippier
Mitochondrial complex II (CII) is an emerging target for numerous human diseases. Sixteen analogues of the CII inhibitor natural product atpenin A5 were prepared to evaluate the structure-activity relationship of the C-5 pyridine side chain. The side chain ketone moiety was determined to be pharmacophoric, engendering a bioactive conformation. Analogue 16c displayed CII IC50 = 64 nM, retained selectivity for CII over mitochondrial complex I (>156-fold) and possessed a ligand-lipophilicity efficiency of 5...
May 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28521807/case-report-a-novel-frameshift-mutation-in-the-mitochondrial-cytochrome-c-oxidase-ii-gene-causing-mitochondrial-disorder
#8
Laura Kytövuori, Mikko Kärppä, Hannu Tuominen, Johanna Uusimaa, Markku Saari, Reetta Hinttala, Kari Majamaa
BACKGROUND: Mitochondrial cytochrome c oxidase 2, MT-CO2, encodes one of the three subunits, which form the catalytic core of cytochrome c oxidase (COX), complex IV. Mutations in MT-CO2 are rare and the associated phenotypes are variable including nonsyndromic and syndromic forms of mitochondrial diseases. CASE PRESENTATION: We describe a 30-year-old man with cognitive decline, epilepsy, psychosis, exercise intolerance, sensorineural hearing impairment, retinitis pigmentosa, cataract and lactic acidosis...
May 18, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28515690/brain-renin-angiotensin-system-and-microglial-polarization-implications-for-aging-and-neurodegeneration
#9
REVIEW
Jose L Labandeira-Garcia, Ana I Rodríguez-Perez, Pablo Garrido-Gil, Jannette Rodriguez-Pallares, Jose L Lanciego, Maria J Guerra
Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28513634/mitochondria-targeted-platinum-ii-complexes-dual-inhibitory-activities-on-tumor-cell-proliferation-and-migration-invasion-via-intracellular-trafficking-of-%C3%AE-catenin
#10
Jingling Li, Xiaoli He, Yeling Zou, Dandan Chen, Liecheng Yang, Jiaming Rao, Huabing Chen, Michael C W Chan, Lin Li, Zhengqing Guo, Leshuai W Zhang, Chunying Chen
Mitochondria-targeted therapy is an alternative strategy for cancer therapy and may overcome the problems of metastasis and drug resistance that usually occur in conventional treatment. In this work, we demonstrate the mitochondria-targeted delivery of a cationic cyclometalated platinum(ii) complex, PIP-platin, in cancer cells. PIP-platin showed selective delivery and accumulation in the mitochondria and exhibited toxicity against a variety of tumor cell lines. The mitochondria were disrupted by PIP-platin, along with the generation of reactive oxygen species, depolarization of mitochondrial membrane potential, release of cytochrome c and necrosis...
May 17, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28511064/design-synthesis-and-evaluation-of-anticancer-activity-of-ruthenium-ii-polypyridyl-complexes
#11
Bing Tang, Dan Wan, Shang-Hai Lai, Hui-Hui Yang, Cheng Zhang, Xiu-Zhen Wang, Chuan-Chuan Zeng, Yun-Jun Liu
A new ligand PFPIP (PFPIP=2-(2,3,4,5,6-pentafluorophenyl)[4,5-f]imadazo [1,10]phenanthroline) and its four ruthenium(II) polypyridyl complexes [Ru(NN)2(PFPIP)](ClO4)2 (NN=dmb: 4,4'-dimethyl-2,2'-bipyridine, 1; bpy: 2,2'-bipyridine, 2; phen: 1,10-phenanthroline, 3; dmp: 2,9-dimethyl-1,10-phenanthroline, 4) were synthesized and characterized by elemental analysis, IR, (1)H NMR, (13)C NMR and ESI-MS. The cytotoxic activity in vitro of the ligand and complexes toward BEL-7402, A549, HeLa, HepG2 and MG-63 cell lines was evaluated using MTT method (MTT=(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)...
May 10, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28506426/heterogeneity-of-fhf1-related-phenotype-novel-case-with-early-onset-severe-attacks-of-apnea-partial-mitochondrial-respiratory-chain-complex-ii-deficiency-neonatal-onset-seizures-without-neurodegeneration
#12
Nathalie Villeneuve, Affef Abidi, Pierre Cacciagli, Cécile Mignon-Ravix, Brigitte Chabrol, Laurent Villard, Mathieu Milh
INTRODUCTION/OBJECTIVES: We report the case of a child prospectively followed in our institution for a severe, neonatal onset epilepsy presenting with severe attacks of apnea that were not initially recognized as seizure since they were not associated with any abnormal movement and since interictal EEG was normal. Recording of attacks using prolonged video-EEG recording allowed to confirm the diagnosis of epileptic seizures. RESULTS: Using whole exome sequencing we found a de novo heterozygous, missense mutation of FHF1 (p...
April 29, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/28504877/illuminating-superoxide-anion-and-ph-enhancements-in-apoptosis-of-breast-cancer-cells-induced-by-mitochondrial-hyperfusion-using-a-new-two-photon-fluorescence-probe
#13
Wen Zhang, Xin Wang, Ping Li, Haibin Xiao, Wei Zhang, Hui Wang, Bo Tang
Mitochondrial morphology regulated by fusion and fission processes determines mitochondrial function and cell fate. Some studies showed hyperfused mitochondria could induce apoptosis in cancer cells, but the relevant molecular mechanisms remain elusive. Superoxide (O2(•-)) and pH play vital roles in mitochondrial dysfunction and apoptosis. Therefore, it is worthwhile to explore if there is an intimate relationship between mitochondrial hyperfusion and simultaneous changes in O2(•-) and pH levels, which will be helpful to uncover relevant detailed mechanism...
May 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28502800/microrna-211-regulates-oxidative-phosphorylation-and-energy-metabolism-in-human-vitiligo
#14
Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J Perera
Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing (RNA-seq), targeted metabolomics, and shotgun lipidomics...
May 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28500267/impaired-mitochondrial-transcription-termination-disrupts-the-stromal-redox-poise-in-chlamydomonas
#15
Andreas Uhmeyer, Matteo Ballottari, Michela Cecchin, Lutz Wobbe
In photosynthetic eukaryotes, the metabolite exchange between chloroplast and mitochondria ensures efficient photosynthesis under saturating light conditions. The C. reinhardtii mutant stm6 is devoid of the mitochondrial transcription termination factor (mTERF) MOC1 and aberrantly expresses the mitochondrial genome, resulting in enhanced photosynthetic hydrogen production and diminished light tolerance. We analyzed the modulation of mitochondrial and chlororespiration during the acclimation of stm6 and the MOC1-complemented strain to excess light...
May 12, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28499395/time-course-of-blood-lactate-levels-inflammation-and-mitochondrial-function-in-experimental-sepsis
#16
Thiago Domingos Corrêa, Adriano José Pereira, Sebastian Brandt, Madhusudanarao Vuda, Siamak Djafarzadeh, Jukka Takala, Stephan Mathias Jakob
BACKGROUND: A decrease in blood lactate levels (Lac) >10% during the first hours of resuscitation in sepsis is associated with better outcomes, but the mechanisms are unclear. Our objective was to investigate the relationship between the time course of Lac, inflammatory response, and mitochondrial respiration during experimental sepsis. METHODS: Original data from two previously published studies were reanalyzed. In cohort 1, pigs were randomized to be resuscitated for 48 h starting at 6, 12, and 24 h, respectively, after fecal peritonitis induction (n = 8 each)...
May 12, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28483572/early-energy-metabolism-related-molecular-events-in-skeletal-muscle-of-diabetic-rats-the-effects-of-l-arginine-and-sod-mimic
#17
Ana Stancic, Milos Filipovic, Ivana Ivanovic-Burmazovic, Sava Masovic, Aleksandra Jankovic, Vesna Otasevic, Aleksandra Korac, Biljana Buzadzic, Bato Korac
Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days...
May 5, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28479248/effects-of-non-invasive-remote-ischemic-conditioning-on-rehabilitation-after-myocardial-infarction
#18
Meng-Yao An, Yan Li, Wen-Hua Chen, Ying Zhang, Yan-Na Wu, Kai Sun, Ying-Ying Pan, Yong-Qiang Yin, Jian-Shi Lou
Recent studies have demonstrated that remote ischemic conditioning (RIC) creates cardioprotection against ischemia/reperfusion injury and myocardial infarction (MI); however, the effects of non-invasive remote ischemic conditioning (nRIC) on prognosis and rehabilitation after MI (post-MI) remain unknown. We successfully established MI models involving healthy adult male Sprague-Dawley rats. The nRIC group repeatedly underwent 5 min of ischemia and 5 min of reperfusion in the left hind limb for three cycles every other day until weeks 4, 6, and 8 after MI...
May 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28474567/reduced-mitochondrial-activity-is-early-and-steady-in-the-entorhinal-cortex-but-it-is-mainly-unmodified-in-the-frontal-cortex-in-alzheimer-s-disease
#19
Mercedes Armand-Ugon, Belen Ansoleaga, Sara Berjaoui, Isidro Ferrer
Background It is well established that mitochondrial damage plays a role in the pathophysiology of Alzheimer's disease (AD). However, studies carried out in humans barely contemplate regional differences with disease progression. Objective To study the expression of selected nuclear genes encoding subunits of the mitochondrial complexes and the activity of mitochondrial complexes in AD, in two regions: the entorhinal cortex (EC) and frontal cortex area 8 (FC). Methods Frozen samples from 148 cases processed for gene expression by qRT-PCR and determination of individual activities of mitochondrial complexes I, II, IV and V using commercial kits and home-made assays...
May 4, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28472853/genetic-rescue-of-mitochondrial-and-skeletal-muscle-impairment-in-an-induced-pluripotent-stem-cells-model-of-coenzyme-q10-deficiency
#20
Damià Romero-Moya, Carlos Santos-Ocaña, Julio Castaño, Gloria Garrabou, José A Rodríguez-Gómez, Vanesa Ruiz-Bonilla, Clara Bueno, Patricia González-Rodríguez, Alessandra Giorgetti, Eusebio Perdiguero, Cristina Prieto, Constanza Moren-Nuñez, Daniel J Fernández-Ayala, Maria Victoria Cascajo, Iván Velasco, Josep Maria Canals, Raquel Montero, Delia Yubero, Cristina Jou, José López-Barneo, Francesc Cardellach, Pura Muñoz-Cánoves, Rafael Artuch, Plácido Navas, Pablo Menendez
Coenzyme Q10 (CoQ10 ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC) and is an essential antioxidant. Mutations in genes responsible for CoQ10 biosynthesis (COQ genes) cause primary CoQ10 deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype-phenotype association, mainly affecting tissues with high-energy demand including brain and skeletal muscle (SkM). Here, we report a four-year-old girl diagnosed with minor mental retardation and lethal rhabdomyolysis harboring a heterozygous mutation (c...
May 4, 2017: Stem Cells
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