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Coenzyme q

Ruinan Gu, Fali Zhang, Gang Chen, Chaojun Han, Jay Liu, Zhaoxiang Ren, Yi Zhu, John L Waddington, Long Tai Zheng, Xuechu Zhen
Clock (Clk)1/COQ7 is a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone (coenzyme Q or UQ). Here, we investigate the role of Clk1 in neuroinflammation and consequentially dopaminergic (DA) neuron survival. Reduced expression of Clk1 in microglia enhanced the LPS-induced proinflammatory response and promoted aerobic glycolysis. Inhibition of glycolysis abolished Clk1 deficiency-induced hypersensitivity to the inflammatory stimulation. Mechanistic studies demonstrated that mTOR/HIF-1α and ROS/HIF-1α signaling pathways were involved in Clk1 deficiency-induced aerobic glycolysis...
October 18, 2016: Brain, Behavior, and Immunity
Andrzej M Woyda-Ploszczyca, Wieslawa Jarmuszkiewicz
Uncoupling proteins (UCPs) belong to the mitochondrial anion carrier protein family and mediate regulated proton leak across the inner mitochondrial membrane. Free fatty acids, aldehydes such as hydroxynonenal, and retinoids activate UCPs. However, there are some controversies about the effective action of retinoids and aldehydes alone; thus, only free fatty acids are commonly accepted positive effectors of UCPs. Conversely, purine nucleotides such as GTP inhibit UCP-mediated mitochondrial proton leak. In turn, membranous coenzyme Q may play a role as a redox state-dependent metabolic sensor that modulates the complete activation/inhibition of UCPs...
October 14, 2016: Biochimica et Biophysica Acta
Josef Finsterer, Sinda Zarrouk-Mahjoub
No abstract text is available yet for this article.
October 12, 2016: Cornea
Dan Zhang, Kiera Robinson, Doina M Mihai, Ilyas Washington
Animals alter their physiological states in response to their environment. We show that the introduction of a chlorophyll metabolite, a light-absorbing pigment widely consumed in human diets, to Caenorhabditis elegans results in animals whose fat mass can be modulated by exposure to light, despite the worm consuming the same amount of food. In the presence of the chlorophyll metabolite, exposing the worms to light increased adenosine triphosphate, reduced oxidative damage, and increased median life spans, without an effect on animal reproduction...
October 12, 2016: Scientific Reports
A K Datta, S Campbell, B Deval, G Nargund
A series of new technologies and adjuvant therapies have been advocated in order to improve the success of IVF treatment. Dehydro-epiandrostenedione, growth hormones, Coenzyme Q 10, calcium ionosphores, immune therapy, heparin, low-dose aspirin, and vasodilators are among commonly prescribed pharmacological adjuvants. New technologies that are proposed to improve IVF outcomes include advanced sperm selection procedures, time- lapse embryo monitoring, preimplantation genetic screening, assisted hatching endometrial injury or embryo-glue...
December 28, 2015: Facts, Views & Vision in ObGyn
Y-X Kang, Y-J Wang, Q Zhang, X-H Pang, W Gu
Kearns-Sayre syndrome (KSS) is a disorder caused by mutations in mitochondrial DNA. Here, we report an unusual case of Kearns-Sayre syndrome accompanied by hypopituitarism (deficiencies in reproductive and growth hormones). A 20-year-old male presented with growth retardation for the last 8 years, as well as the following findings: short stature, delayed puberty, myasthenia, an extraocular movement deficit, drooping eyelids, pectus carinatum and scoliosis. Cerebral enhanced magnetic resonance imaging revealed dysplasias of the pituitary, white matter and cerebellum...
October 6, 2016: Andrologia
Laurie-Anne Payet, Mélanie Leroux, John C Willison, Akio Kihara, Ludovic Pelosi, Fabien Pierrel
Coenzyme Q (Q) is a redox lipid that is central for the energetic metabolism of eukaryotes. The biosynthesis of Q from the aromatic precursor 4-hydroxybenzoic acid (4-HB) is understood fairly well. However, biosynthetic details of how 4-HB is produced from tyrosine remain elusive. Here, we provide key insights into this long-standing biosynthetic problem by uncovering molecular details of the first and last reactions of the pathway in the yeast Saccharomyces cerevisiae, namely the deamination of tyrosine to 4-hydroxyphenylpyruvate by Aro8 and Aro9, and the oxidation of 4-hydroxybenzaldehyde to 4-HB by Hfd1...
October 20, 2016: Cell Chemical Biology
Tibor András Rokob
Oxygenation of aromatic rings using O2 is catalyzed by several non-heme carboxylate-bridged diiron enzymes. In order to provide a general mechanistic description for these reactions, computational studies were carried out at the ONIOM(B3LYP/BP86/Amber) level on the non-heme diiron enzyme benzoyl coenzyme A epoxidase BoxB. The calculations revealed four possible pathways for attacking the aromatic ring: a) electrophilic (2e(-)) attack by a bis(μ-oxo)-diiron(IV) species (Q pathway); b) electrophilic (2e(-)) attack via the σ* orbital of a μ-η(2):η(2)-peroxo-diiron(III) intermediate (Pσ* pathway); c) radical (1e(-)) attack via the π*-orbital of a superoxo-diiron(II,III) species (Pπ* pathway); d) radical (1e(-)) attack of a partially quenched diiron(IV) intermediate (Q' pathway)...
September 28, 2016: Journal of the American Chemical Society
Jonathan A Stefely, Nicholas W Kwiecien, Elyse C Freiberger, Alicia L Richards, Adam Jochem, Matthew J P Rush, Arne Ulbrich, Kyle P Robinson, Paul D Hutchins, Mike T Veling, Xiao Guo, Zachary A Kemmerer, Kyle J Connors, Edna A Trujillo, Jacob Sokol, Harald Marx, Michael S Westphall, Alexander S Hebert, David J Pagliarini, Joshua J Coon
Mitochondrial dysfunction is associated with many human diseases, including cancer and neurodegeneration, that are often linked to proteins and pathways that are not well-characterized. To begin defining the functions of such poorly characterized proteins, we used mass spectrometry to map the proteomes, lipidomes, and metabolomes of 174 yeast strains, each lacking a single gene related to mitochondrial biology. 144 of these genes have human homologs, 60 of which are associated with disease and 39 of which are uncharacterized...
September 26, 2016: Nature Biotechnology
Laura Astolfi, Edi Simoni, Filippo Valente, Sara Ghiselli, Stavros Hatzopoulos, Milvia Chicca, Alessandro Martini
Cisplatin (Cpt) is known to induce a high level of oxidative stress, resulting in an increase of reactive oxygen species damaging the inner ear and causing hearing loss at high frequencies. Studies on animal models show that antioxidants may lower Cpt-induced ototoxicity. The aim of this study is to evaluate the ototoxic effects of two different protocols of Cpt administration in a Sprague-Dawley rat model, and to test in the same model the synergic protective effects of a solution of coenzyme Q10 terclatrate and Acuval 400®, a multivitamin supplement containing antioxidant agents and minerals (Acu-Qter)...
2016: PloS One
Ablat Tursun, Shaotong Zhu, Steven B Vik
Respiratory Complex I appears to have 4 sites for proton translocation, which are coupled to the oxidation of NADH and reduction of coenzyme Q. The proton pathways are thought to be made of offset half-channels that connect to the membrane surfaces, and are connected by a horizontal path through the center of the membrane. In this study of the enzyme from Escherichia coli, subunit N, containing one of the sites, was targeted. Pairs of cysteine residues were introduced into neighboring α-helices along the proposed proton pathways...
September 12, 2016: Biochimica et Biophysica Acta
Chetan Purushottam Raut, Kunal S Sethi
BACKGROUND: Conventional nonsurgical periodontal therapy has been proven to be an effective treatment for patients with chronic periodontitis. Coenzyme Q10 and tea tree oil (TTO) are known to have potential therapeutic benefits in chronic periodontitis. AIMS: The aim of the study is to compare the efficacy of Coenzyme Q10 (Perio Q(®)) and tea tree oil (Melaleuca alternifolia) gel as an adjunct to scaling and root planing in the treatment of chronic periodontitis...
July 2016: Contemporary Clinical Dentistry
Wenbin Shen, Xiao Ren, Jingtong Zhu, Yan Xu, Jie Lin, Yeying Li, Feng Zhao, Haizhou Zheng, Ruolan Li, Xiaolan Cui, Xuexia Zhang, Xinhua Lu, Zhihui Zheng
Human dihydroorotate dehydrogenase (hDHODH) is an inner mitochondrial membrane enzyme that involves in the fourth step of the biosynthesis of pyrimidine base. Inhibitors of hDHODH have been proven efficacy for the treatments of inflammation, rheumatoid arthritis, multiple sclerosis and cancer. In the present study, ascochlorin (ASC) and its derivatives, natural compounds from fungal metabolites, were discovered as hDHODH inhibitors by high-throughput screening. Enzyme kinetics studies showed that ASC competitively binds to hDHODH at the site of coenzyme Q substrate...
September 3, 2016: European Journal of Pharmacology
Jerzy A Zoladz, Agnieszka Koziel, Andrzej Woyda-Ploszczyca, Jan Celichowski, Wieslawa Jarmuszkiewicz
Endurance training enhances mitochondrial oxidative capacity, but its effect on mitochondria functioning is poorly understood. In the present study, the influence of an 8-week endurance training on the bioenergetic functioning of rat skeletal muscle mitochondria under different assay temperatures (25, 35, and 42 °C) was investigated. The study was performed on 24 adult 4-month-old male Wistar rats, which were randomly assigned to either a treadmill training group (n = 12) or a sedentary control group (n = 12)...
October 2016: Pflügers Archiv: European Journal of Physiology
Jin Wang, Fei Xia, Wen-Bin Jin, Jin-Yan Guan, Hang Zhao
A new strategy for the efficient synthesis of C-5 heterocyclyl substituted Coenzyme Q analogues was developed by N-alkylation of bromomethylated quinone 11 with a series of amines 12 under metal-free conditions. In vitro antioxidant activities of these Coenzyme Q analogues were evaluated and compared with commercial antioxidant Coenzyme Q10 by employing DPPH assay. All these N-heterocyclyl substituted Coenzyme Q analogues are found to be exhibiting good antioxidant properties and may be used as potent antioxidants for combating oxidative stress...
October 2016: Bioorganic Chemistry
Maedeh Moradi, Fahimeh Haghighatdoost, Awat Feizi, Bagher Larijani, Leila Azadbakht
BACKGROUND: Several studies have investigated the effect of Co-Q10 on diabetes biomarkers, but findings are inconsistent. This systematic review and meta-analysis of clinical trials was conducted to summarize the effect of Co-Q10 supplementation on diabetes biomarkers. METHODS: We searched Pubmed, EMBASE, Science direct, ISI web of science, and Google Scholar for randomized controlled trials from 1989 until March 2016. We included randomized controlled trials reporting fasting blood glucose (FBG), fasting insulin and HbA1c...
August 2016: Archives of Iranian Medicine
Kimberly L James, Luis A Ríos-Hernández, Neil Q Wofford, Housna Mouttaki, Jessica R Sieber, Cody S Sheik, Hong H Nguyen, Yanan Yang, Yongming Xie, Jonathan Erde, Lars Rohlin, Elizabeth A Karr, Joseph A Loo, Rachel R Ogorzalek Loo, Gregory B Hurst, Robert P Gunsalus, Luke I Szweda, Michael J McInerney
UNLABELLED: Syntrophus aciditrophicus is a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation by S. aciditrophicus However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome of S. aciditrophicus leaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate...
2016: MBio
Brendan J Floyd, Emily M Wilkerson, Mike T Veling, Catie E Minogue, Chuanwu Xia, Emily T Beebe, Russell L Wrobel, Holly Cho, Laura S Kremer, Charlotte L Alston, Katarzyna A Gromek, Brendan K Dolan, Arne Ulbrich, Jonathan A Stefely, Sarah L Bohl, Kelly M Werner, Adam Jochem, Michael S Westphall, Jarred W Rensvold, Robert W Taylor, Holger Prokisch, Jung-Ja P Kim, Joshua J Coon, David J Pagliarini
Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor...
August 18, 2016: Molecular Cell
Jonathan A Stefely, Floriana Licitra, Leila Laredj, Andrew G Reidenbach, Zachary A Kemmerer, Anais Grangeray, Tiphaine Jaeg-Ehret, Catherine E Minogue, Arne Ulbrich, Paul D Hutchins, Emily M Wilkerson, Zheng Ruan, Deniz Aydin, Alexander S Hebert, Xiao Guo, Elyse C Freiberger, Laurence Reutenauer, Adam Jochem, Maya Chergova, Isabel E Johnson, Danielle C Lohman, Matthew J P Rush, Nicholas W Kwiecien, Pankaj K Singh, Anna I Schlagowski, Brendan J Floyd, Ulrika Forsman, Pavel J Sindelar, Michael S Westphall, Fabien Pierrel, Joffrey Zoll, Matteo Dal Peraro, Natarajan Kannan, Craig A Bingman, Joshua J Coon, Philippe Isope, Hélène Puccio, David J Pagliarini
The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions...
August 18, 2016: Molecular Cell
Delia Yubero, Raquel Montero, Miguel A Martín, Julio Montoya, Antonia Ribes, Manuela Grazina, Eva Trevisson, Juan Carlos Rodriguez-Aguilera, Iain P Hargreaves, Leonardo Salviati, Plácido Navas, Rafael Artuch, Cristina Jou, Cecilia Jimenez-Mallebrera, Andres Nascimento, Belén Pérez-Dueñas, Carlos Ortez, Federico Ramos, Jaume Colomer, Mar O'Callaghan, Mercè Pineda, Angels García-Cazorla, Carmina Espinós, Angels Ruiz, Alfons Macaya, Anna Marcé-Grau, Judit Garcia-Villoria, Angela Arias, Sonia Emperador, Eduardo Ruiz-Pesini, Ester Lopez-Gallardo, Viruna Neergheen, Marta Simões, Luisa Diogo, Alberto Blázquez, Adrián González-Quintana, Aitor Delmiro, Cristina Domínguez-González, Joaquín Arenas, M Teresa García-Silva, Elena Martín, Pilar Quijada, Aurelio Hernández-Laín, María Morán, Eloy Rivas Infante, Rainiero Ávila Polo, Carmen Paradas Lópe, Juan Bautista Lorite, Eva M Martínez Fernández, Ana B Cortés, Ana Sánchez-Cuesta, Maria V Cascajo, María Alcázar, Gloria Brea-Calvo
We evaluated the coenzyme Q₁₀ (CoQ) levels in patients who were diagnosed with mitochondrial oxidative phosphorylation (OXPHOS) and non-OXPHOS disorders (n=72). Data from the 72 cases in this study revealed that 44.4% of patients showed low CoQ concentrations in either their skeletal muscle or skin fibroblasts. Our findings suggest that secondary CoQ deficiency is a common finding in OXPHOS and non-OXPHOS disorders. We hypothesize that cases of CoQ deficiency associated with OXPHOS defects could be an adaptive mechanism to maintain a balanced OXPHOS, although the mechanisms explaining these deficiencies and the pathophysiological role of secondary CoQ deficiency deserves further investigation...
September 2016: Mitochondrion
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