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https://www.readbyqxmd.com/read/29147009/mitochondrial-uqcrb-as-a-new-molecular-prognostic-biomarker-of-human-colorectal-cancer
#1
Hyun-Chul Kim, Junghwa Chang, Hannah S Lee, Ho Jeong Kwon
Ubiquinol cytochrome c reductase binding protein (UQCRB) is important for mitochondrial complex III stability, electron transport, cellular oxygen sensing and angiogenesis. However, its potential as a prognostic marker in colorectal cancer (CRC) remains unclear. The aim of this study was to determine whether UQCRB can be used as a diagnostic molecular marker for CRC. The correlation between the expression of three genes (UQCRB, UQCRFS1 and MT-CYB) in the mitochondrial respiratory chain complex III and clinico-pathological features was determined...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29138850/role-of-mitochondrial-function-in-the-invasiveness-of-human-colon-cancer-cells
#2
Chen-Sung Lin, Li-Tzu Liu, Liang-Hung Ou, Siao-Cian Pan, Chia-I Lin, Yau-Huei Wei
We investigated the role of mitochondrial function in the invasiveness of human colorectal cancer (CRC) cell lines, using paired primary SW480 and metastatic SW620 cells, and appraised the clinical relevance of the alteration of mtDNA copy number in 33 pairs of CRC specimens after surgical resection. Suppression of mitochondrial function was achieved by the exposure of cells to oligomycin A (OA) or by knockdown of mitochondrial transcriptional factor A (TFAM) to evaluate their effects on energy metabolism, reactive oxygen species, protein expression levels of epithelial-mesenchymal transition (EMT) markers and invasive activity of CRC cells...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29133414/correlating-kinetic-and-structural-data-on-ubiquinone-binding-and-reduction-by-respiratory-complex-i
#3
Justin G Fedor, Andrew J Y Jones, Andrea Di Luca, Ville R I Kaila, Judy Hirst
Respiratory complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in mammalian cells, powers ATP synthesis by using the energy from electron transfer from NADH to ubiquinone-10 to drive protons across the energy-transducing mitochondrial inner membrane. Ubiquinone-10 is extremely hydrophobic, but in complex I the binding site for its redox-active quinone headgroup is ∼20 Å above the membrane surface. Structural data suggest it accesses the site by a narrow channel, long enough to accommodate almost all of its ∼50-Å isoprenoid chain...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29126780/identification-of-protein-w-the-elusive-sixth-subunit-of-the-rhodopseudomonas-palustris-reaction-center-light-harvesting-1-core-complex
#4
Philip J Jackson, Andrew Hitchcock, David J K Swainsbury, Pu Qian, Elizabeth C Martin, David A Farmer, Mark J Dickman, Daniel P Canniffe, C Neil Hunter
The X-ray crystal structure of the Rhodopseudomonas (Rps.) palustris reaction center-light harvesting 1 (RC-LH1) core complex revealed the presence of a sixth protein component, variably referred to in the literature as helix W, subunit W or protein W. The position of this protein prevents closure of the LH1 ring, possibly to allow diffusion of ubiquinone/ubiquinol between the RC and the cytochrome bc1 complex in analogous fashion to the well-studied PufX protein from Rhodobacter sphaeroides. The identity and function of helix W have remained unknown for over 13 years; here we use a combination of biochemistry, mass spectrometry, molecular genetics and electron microscopy to identify this protein as RPA4402 in Rps...
November 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29115404/downregulation-of-mitochondrial-uqcrb-inhibits-cancer-stem-cell-like-properties-in-glioblastoma
#5
Narae Jung, Ho Jeong Kwon, Hye Jin Jung
Glioblastoma stem cell targeted therapies have become a powerful strategy for the treatment of this deadliest brain tumor. We demonstrate for the first time that downregulation of mitochondrial ubiquinol-cytochrome c reductase binding protein (UQCRB) inhibits the cancer stem cell-like properties in human glioblastoma cells. The synthetic small molecules targeting UQCRB significantly suppressed not only the self-renewal capacity such as growth and neurosphere formation, but also the metastatic potential such as migration and invasion of glioblastoma stem‑like cells (GSCs) derived from U87MG and U373MG at subtoxic concentrations...
November 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29107420/african-trypanosomiasis-synthesis-sar-enabling-novel-drug-discovery-of-ubiquinol-mimics-for-trypanosome-alternative-oxidase
#6
Ryan A West, Oran G O'Doherty, Trevor Askwith, John Atack, Paul Beswick, Jamie Laverick, Michael Paradowski, Lewis E Pennicott, Srinivasa P S Rao, Gareth Williams, Simon E Ward
African trypanosomiasis is a parasitic disease affecting 5000 humans and millions of livestock animals in sub-Saharan Africa every year. Current treatments are limited, difficult to administer and often toxic causing long term injury or death in many patients. Trypanosome alternative oxidase is a parasite specific enzyme whose inhibition by the natural product ascofuranone (AF) has been shown to be curative in murine models. Until now synthetic methods to AF analogues have been limited, this has restricted both understanding of the key structural features required for binding and also how this chemotype could be developed to an effective therapeutic agent...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29021617/imaging-mass-spectrometry-analysis-of-ubiquinol-localization-in-the-mouse-brain-following-short-term-administration
#7
Yukina Tatsuta, Kazuaki Kasai, Chitose Maruyama, Yoshimitsu Hamano, Kazuhiko Matsuo, Hajime Katano, Shu Taira
We analyzed the localization of ubiquinol, the reduced form of coenzyme Q10 (Re-CoQ10), in mouse brain sections using matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance imaging mass spectrometry (IMS) to evaluate the effect of dietary Re-CoQ10 in mouse brain. Mice were orally administered Re-CoQ10 for 14 days and brain Re-CoQ10 content was subsequently quantified using liquid chromatography-mass spectrometry. IMS was employed to visualize Re-CoQ10 at a resolution of 150 μm in the mouse brain...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28986235/alpha-synuclein-epigenetics-mitochondria-metabolism-calcium-traffic-circadian-dysfunction-in-parkinson-s-disease-an-integrated-strategy-for-management
#8
REVIEW
Oliver T Phillipson
The motor deficits which characterise the sporadic form of Parkinson's disease arise from age-related loss of a subset of dopamine neurons in the substantia nigra. Although motor symptoms respond to dopamine replacement therapies, the underlying disease process remains. This review details some features of the progressive molecular pathology and proposes deployment of a combination of nutrients: R-lipoic acid, acetyl-l-carnitine, ubiquinol, melatonin (or receptor agonists) and vitamin D3, with the collective potential to slow progression of these features...
November 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28978450/analysis-of-a-functional-dimer-model-of-ubiquinol-cytochrome-c-oxidoreductase
#9
Jason N Bazil
Ubiquinol cytochrome c oxidoreductase (bc1 complex) serves as an important electron junction in many respiratory systems. It funnels electrons coming from NADH and ubiquinol to cytochrome c, but it is also capable of producing significant amounts of the free radical superoxide. In situ and in other experimental systems, the enzyme exists as a dimer. But until recently, it was believed to operate as a functional monomer. Here we show that a functional dimer model is capable of explaining both kinetic and superoxide production rate data...
October 3, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28967163/mild-phenotypes-and-proper-supercomplex-assembly-in-human-cells-carrying-the-homoplasmic-m-15557g%C3%A2-%C3%A2-a-mutation-in-cytochrome-b-gene
#10
Luisa Iommarini, Anna Ghelli, Giulia Leone, Concetta Valentina Tropeano, Ivana Kurelac, Laura Benedetta Amato, Giuseppe Gasparre, Anna Maria Porcelli
Respiratory complex III (CIII) is the first enzymatic bottleneck of the mitochondrial respiratory chain both in its native dimeric form and in supercomplexes. The mammalian CIII comprises 11 subunits among which cytochrome b is central in the catalytic core, where oxidation of ubiquinol occurs at the Qo site. The Qo- or PEWY-motif of cytochrome b is the most conserved through species. Importantly, the highly conserved glutamate at position 271 (Glu271) has never been studied in higher eukaryotes so far and its role in the Q-cycle remains debated...
October 1, 2017: Human Mutation
https://www.readbyqxmd.com/read/28943100/validation-of-a-pharmacological-model-for-mitochondrial-dysfunction-in-healthy-subjects-using-simvastatin-a-randomized-placebo-controlled-proof-of-pharmacology-study
#11
Marcus P J van Diemen, Cécile L Berends, Naila Akram, Joep Wezel, Wouter M Teeuwisse, Bert G Mik, Hermien E Kan, Andrew Webb, Jan Willem M Beenakker, Geert Jan Groeneveld
Proof-of-pharmacology models to study compounds in healthy subjects offer multiple advantages. Simvastatin is known to induce mitochondrial dysfunction at least partly by depletion of co-enzyme Q10. The goal of this study was to evaluate a model of simvastatin-induced mitochondrial dysfunction in healthy subjects and to determine whether mitochondrial dysfunction could be pharmacologically reversed by treatment with co-enzyme Q10 (ubiquinol). Subjects received simvastatin 40mg/day for 8 weeks. After 4 weeks, subjects were randomized to receive ubiquinol 300mg/day or placebo in a double-blinded fashion...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28921079/identification-of-a-new-isoindole-2-yl-scaffold-as-a-qo-and-qi-dual-inhibitor-of-cytochrome-bc-1-complex-virtual-screening-synthesis-and-biochemical-assay
#12
Homa Azizian, Kowsar Bagherzadeh, Sophia Shahbazi, Niusha Sharifi, Massoud Amanlou
Respiratory chain ubiquinol-cytochrome (cyt) c oxidoreductase (cyt bc 1 or complex III) has been demonstrated as a promising target for numerous antibiotics and fungicide applications. In this study, a virtual screening of NCI diversity database was carried out in order to find novel Qo/Qi cyt bc 1 complex inhibitors. Structure-based virtual screening and molecular docking methodology were employed to further screen compounds with inhibition activity against cyt bc 1 complex after extensive reliability validation protocol with cross-docking method and identification of the best score functions...
September 18, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28883650/a-novel-and-stress-adaptive-alternative-oxidase-derived-from-alternative-splicing-of-duplicated-exon-in-oyster-crassostrea-virginica
#13
Ming Liu, Ximing Guo
Alternative oxidase (AOX) is a mitochondrial inner-membrane oxidase that accepts electrons directly from ubiquinol and reduces oxygen to water without involving cytochrome-linked electron transport chain. It is highly conserved in many non-vertebrate taxa and may protect cells against hypoxia and oxidative stress. We identified two AOX mRNAs in eastern oyster Crassostrea virginica, CvAOXA and CvAOXB, which differ by 170 bp but encode AOXs of the same size. Sequence analyses indicate that CvAOX has 10 exons with a tandem duplication of exon 10, and 3' alternative splicing using either the first or second exon 10 produces the two variants CvAOXB or CvAOXA, respectively...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28755974/a-pilot-study-exploring-the-effects-of-ubiquinol-on-brain-genomics-after-traumatic-brain-injury
#14
Janet D Pierce, Qiuhua Shen, Jill Peltzer, Amanda Thimmesch, John B Hiebert
BACKGROUND: Traumatic brain injury is a major cause of morbidity and mortality that affects military service members and veterans. PURPOSE: Explore the effects of ubiquinol before traumatic brain injury on cerebral gene expression to elucidate molecular mechanisms of ubiquinol neuroprotection. METHOD: In this experimental study, Fisher rats in the untreated (n = 2) and ubiquinol-treated (n = 2) groups received respectively either normal saline or ubiquinol 30 min before traumatic brain injury induced by controlled cortical impact...
September 2017: Nursing Outlook
https://www.readbyqxmd.com/read/28750029/ubiquinol-cytochrome-c-reductase-core-protein-1-may-be-involved-in-delayed-cardioprotection-from-preconditioning-induced-by-diazoxide
#15
Zonghong Long, Guangyou Duan, Hong Li, Tingting Yi, Xiaoxiao Wu, Feng Chen, Zhuoxi Wu, Yuqi Gao
This study aimed to use long-term diazoxide treatment to establish a loss-of-cardioprotection model and then perform proteomics analysis to explore which proteins of mitochondrial inner membrane (MIM) are potentially involved in delayed cardioprotection. Rats received 1 to 8 weeks of diazoxide treatments (20 mg•kg-1•d-1) to establish a loss-of-cardioprotection model in different groups. Detection of serum cTnI levels and cell apoptosis assays in heart tissue were performed. Then, rats MIM after 0, 4 and 6 weeks of diazoxide treatment was isolated and proteomics analysis was performed...
2017: PloS One
https://www.readbyqxmd.com/read/28714002/identification-of-key-genes-in-gram%C3%A2-positive-and-gram%C3%A2-negative-sepsis-using-stochastic-perturbation
#16
Zhenliang Li, Ying Zhang, Yaling Liu, Yanchun Liu, Youyi Li
Sepsis is an inflammatory response to pathogens (such as Gram‑positive and Gram‑negative bacteria), which has high morbidity and mortality in critically ill patients. The present study aimed to identify the key genes in Gram‑positive and Gram‑negative sepsis. GSE6535 was downloaded from Gene Expression Omnibus, containing 17 control samples, 18 Gram‑positive samples and 25 Gram‑negative samples. Subsequently, the limma package in R was used to screen the differentially expressed genes (DEGs). Hierarchical clustering was conducted for the specific DEGs in Gram‑negative and Gram‑negative samples using cluster software and the TreeView software...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28702034/cardr1-an-rna-dependent-rna-polymerase-plays-a-positive-role-in-pepper-resistance-against-tmv
#17
Lei Qin, Ning Mo, Yang Zhang, Tayeb Muhammad, Guiye Zhao, Yan Zhang, Yan Liang
RNA silencing functions as a major natural antiviral defense mechanism in plants. RNA-dependent RNA polymerases (RDRs) that catalyze the synthesis of double-stranded RNAs, are considered as a fundamental element in RNA silencing pathways. In Arabidopsis thaliana, RDR1, 2 and 6 play important roles in anti-viral RNA silencing. Expression of RDR1 can be elevated following plant treatment with defense hormones and virus infection. RDR1 has been studied in several crop species, but not in pepper (Capsicum annuum L...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28701960/role-of-mitochondrial-reverse-electron-transport-in-ros-signaling-potential-roles-in-health-and-disease
#18
REVIEW
Filippo Scialò, Daniel J Fernández-Ayala, Alberto Sanz
Reactive Oxygen Species (ROS) can cause oxidative damage and have been proposed to be the main cause of aging and age-related diseases including cancer, diabetes and Parkinson's disease. Accordingly, mitochondria from old individuals have higher levels of ROS. However, ROS also participate in cellular signaling, are instrumental for several physiological processes and boosting ROS levels in model organisms extends lifespan. The current consensus is that low levels of ROS are beneficial, facilitating adaptation to stress via signaling, whereas high levels of ROS are deleterious because they trigger oxidative stress...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28687989/screening-novel-autoantigens-targeted-by-serum-igg-autoantibodies-in-immunorelated-pancytopenia-by-serex
#19
Shanfeng Hao, Rong Fu, Huaquan Wang, Zonghong Shao
Immunorelated pancytopenia (IRP) is characterized by pancytopenia caused by autoantibody-mediated destruction or suppression of bone marrow. However, the autoantigens targeted by autoantibodies in IRP remain unclear. In the present study, we screened novel autoantigens in IRP by serological analysis of recombinant cDNA expression libraries and compared anti-UQCR10 antibody levels between IRP and normal controls detected by immunoblotting. Our results indicate that we successfully constructed the K562 cDNA library, which we used to screen seven candidate autoantigens expressed in haematopoietic cells of IRP: ferritin, light polypeptide, ubiquinol-cytochrome c reductase, complex III subunit X (UQCR10), multifunctional methyl-transferase subunit TRM112-like protein isoform 1 (TRMT112), hemoglobin gamma-G, stathmin 1 (STMN1), transcript variant 3, phosphoglycerate kinase 1 (PGK1), and trafficking protein particle complex subunit 4 (TRAPPC4)...
November 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28684614/ubiquinol-effects-on-antiphospholipid-syndrome-prothrombotic-profile-a-randomized-placebo-controlled-trial
#20
RANDOMIZED CONTROLLED TRIAL
Carlos Pérez-Sánchez, María Ángeles Aguirre, Patricia Ruiz-Limón, María Carmen Ábalos-Aguilera, Yolanda Jiménez-Gómez, Iván Arias-de la Rosa, Antonio Rodriguez-Ariza, Lucía Fernández-Del Río, José Antonio González-Reyes, Pedro Segui, Eduardo Collantes-Estévez, Nuria Barbarroja, Francisco Velasco, Savino Sciascia, Irene Cecchi, María José Cuadrado, José Manuel Villalba, Chary López-Pedrera
OBJECTIVE: Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10 [Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial...
October 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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