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https://www.readbyqxmd.com/read/29789531/mitochondrial-oxphos-influences-immune-cell-fate-lessons-from-hematopoietic-aif-deficient-and-ndufs4-deficient-mouse-models
#1
Audrey Bertaux, Lauriane Cabon, Marie-Noëlle Brunelle-Navas, Sandrine Bouchet, Ivan Nemazanyy, Santos A Susin
No abstract text is available yet for this article.
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29784452/regulation-of-the-oxidative-balance-with-coenzyme-q10-sensitizes-human-glioblastoma-cells-to-radiation-and-temozolomide
#2
Javier Frontiñán-Rubio, Raquel María Santiago-Mora, Consuelo María Nieva-Velasco, Gustavo Ferrín, Alicia Martínez-González, María Victoria Gómez, María Moreno, Julia Ariza, Eva Lozano, Jacinto Arjona-Gutiérrez, Antonio Gil-Agudo, Manuel De la Mata, Milica Pesic, Juan Ramón Peinado, José M Villalba, Luis Pérez-Romasanta, Víctor M Pérez-García, Francisco J Alcaín, Mario Durán-Prado
OBJECTIVES: To investigate how the modulation of the oxidative balance affects cytotoxic therapies in glioblastoma, in vitro. MATERIAL AND METHODS: Human glioblastoma U251 and T98 cells and normal astrocytes C8D1A were loaded with coenzyme Q10 (CoQ). Mitochondrial superoxide ion (O2 - ) and H2 O2 were measured by fluorescence microscopy. OXPHOS performance was assessed in U251 cells with an oxytherm Clark-type electrode. Radio- and chemotherapy cytotoxicity was assessed by immunostaining of γH2AX (24 h), annexin V and nuclei morphology, at short (72 h) and long (15 d) time...
May 18, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29774995/-study-on-the-relationship-between-mct-1-and-p53-in-laryngeal-squamous-cell-carcinoma
#3
Y B Wang, O Xu, R J Zhang, C G Shan
Objective: The aim of this study is to investigate the expression and clinical significance of monocarboxylate transporter 1 (MCT-1) and p53 in laryngeal squamous cell carcinoma (LSCC). Method: Immunohistochemical staining of MCT-1 and p53 was carried out in 41 cases of laryngeal squamous cell carcinoma embedded in paraffin, and the relationship between positive expression and clinicopathological data was evaluated. All data were analyzed by SPSS software (Windows version 21.0). Result: In normal mucosa p53 expression was absent; while, the basal "stem cell" layer is highly enriched in MCT-1...
June 5, 2017: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29769197/cancer-associated-fibroblasts-drive-glycolysis-in-a-targetable-signaling-loop-implicated-in-head-and-neck-squamous-cell-carcinoma-progression
#4
Dhruv Kumar, Jacob New, Vikalp Vishwakarma, Radhika Joshi, Jonathan Enders, Fangchen Lin, Sumana Dasari, Wade R Gutierrez, George Leef, Sivapriya Ponnurangam, Hemantkumar Chavan, Lydia Ganaden, Mackenzie M Thornton, Hongying Dai, Ossama Tawfik, Jeffrey Straub, Yelizaveta Shnayder, Kiran Kakarala, Terance Ted Tsue, Douglas A Girod, Bennett Van Houten, Shrikant Anant, Partha Krishnamurthy, Sufi Mary Thomas
Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted hepatocyte growth factor (HGF) facilitates HNSCC progression, however very little is known about the role of CAFs in HNSCC metabolism. Here we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29748033/predominant-asymmetrical-stem-cell-fate-outcome-limits-the-rate-of-niche-succession-in-human-colonic-crypts
#5
Craig Stamp, Anze Zupanic, Ashwin Sachdeva, Elizabeth A Stoll, Daryl P Shanley, John C Mathers, Thomas B L Kirkwood, Rakesh Heer, Benjamin D Simons, Doug M Turnbull, Laura C Greaves
Stem cell (SC) dynamics within the human colorectal crypt SC niche remain poorly understood, with previous studies proposing divergent hypotheses on the predominant mode of SC self-renewal and the rate of SC replacement. Here we use age-related mitochondrial oxidative phosphorylation (OXPHOS) defects to trace clonal lineages within human colorectal crypts across the adult life-course. By resolving the frequency and size distribution of OXPHOS-deficient clones, quantitative analysis shows that, in common with mouse, long-term maintenance of the colonic epithelial crypt relies on stochastic SC loss and replacement mediated by competition for limited niche access...
April 25, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29747424/alterations-of-oxidative-phosphorylation-complexes-in-papillary-thyroid-carcinoma
#6
Franz A Zimmermann, Daniel Neureiter, Wolfgang Sperl, Johannes A Mayr, Barbara Kofler
The papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland, with disruptive mutations in mitochondrial complex I subunits reported at very low frequency. Furthermore, metabolic diversity of PTC has been postulated owing to variable messenger RNA (mRNA) expression of genes encoding subunits of the oxidative phosphorylation (OXHPOS) complexes. The aim of the present study was to evaluate the metabolic diversity of the OXPHOS system at the protein level by using immunohistochemical staining...
May 9, 2018: Cells
https://www.readbyqxmd.com/read/29746779/energy-metabolism-drugs-block-triple-negative-breast-metastatic-cancer-cell-phenotype
#7
Silvia Cecilia Pacheco-Velazquez, Diana Xochiquetzal Robledo-Cadena, Ileana Hernández-Reséndiz, Juan Carlos Gallardo-Pérez, Rafael Moreno-Sánchez, Sara Rodríguez-Enríquez
To establish alternative targeted therapies against triple negative (TN) breast cancer, (1) the energy metabolism and (2) the sensitivity of cell growth, migration and invasiveness towards metabolic, canonical and NSAID inhibitors was analyzed in MDA-MB-231 and MDA-MB-468, two TN metastatic breast cancer cell lines, under both normoxia (21% O2) and hypoxia (0.1% O2). For comparative purposes, analysis was also carried out in the less-metastatic breast MCF-7 cancer cells. Under normoxia, oxidative phosphorylation (OxPhos) was significantly higher (2-times) in MDA-MB-468 than in MDA-MB-231 and MCF-7 whereas their glycolytic fluxes and OxPhos and glycolytic protein contents were all similar...
May 10, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29743487/mitochondrial-complex-i-activity-signals-antioxidant-response-through-erk5
#8
Abrar Ul Haq Khan, Nerea Allende-Vega, Delphine Gitenay, Johan Garaude, Dang-Nghiem Vo, Sana Belkhala, Sabine Gerbal-Chaloin, Claire Gondeau, Martine Daujat-Chavanieu, Cécile Delettre, Stefania Orecchioni, Giovanna Talarico, Francesco Bertolini, Alberto Anel, José M Cuezva, Jose A Enriquez, Guillaume Cartron, Charles-Henri Lecellier, Javier Hernandez, Martin Villalba
Oxidative phosphorylation (OXPHOS) generates ROS as a byproduct of mitochondrial complex I activity. ROS-detoxifying enzymes are made available through the activation of their antioxidant response elements (ARE) in their gene promoters. NRF2 binds to AREs and induces this anti-oxidant response. We show that cells from multiple origins performing OXPHOS induced NRF2 expression and its transcriptional activity. The NRF2 promoter contains MEF2 binding sites and the MAPK ERK5 induced MEF2-dependent NRF2 expression...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29735607/mtdna-haplogroup-n9a-increases-the-risk-of-t2dm-by-altering-mitochondrial-function-and-intracellular-mitochondrial-signals
#9
Hezhi Fang, Nianqi Hu, Qiongya Zhao, Bingqian Wang, Huaibin Zhou, Qingzi Fu, Lijun Shen, Xiong Chen, Feixia Shen, Jianxin Lyu
Mitochondrial DNA (mtDNA) haplogroups have been associated with the incidence of type 2 diabetes mellitus (T2DM), however, their underlying role in T2DM remains poorly elucidated. Here, we report that mtDNA haplogroup N9a was associated with an increased risk of T2DM occurrence in Southern China (OR 1.999 [95% CI 1.229-3.251], P = 0.005). By using transmitochondrial technology, we demonstrated that the activity of respiratory chain complexes were lower in the case of mtDNA haplogroup N9a (N9a1 and N9a10a) than in 3 non-N9a haplogroups (D4j, G3a2, and Y1), and that this could lead to alterations in mitochondrial function and mitochondrial redox status...
May 7, 2018: Diabetes
https://www.readbyqxmd.com/read/29731306/absence-of-complex-i-implicates-rearrangement-of-the-respiratory-chain-in-european-mistletoe
#10
Jennifer Senkler, Nils Rugen, Holger Eubel, Jan Hegermann, Hans-Peter Braun
The mitochondrial oxidative phosphorylation (OXPHOS) system, which is based on the presence of five protein complexes, is in the very center of cellular ATP production. Complexes I to IV are components of the respiratory electron transport chain that drives proton translocation across the inner mitochondrial membrane. The resulting proton gradient is used by complex V (the ATP synthase complex) for the phosphorylation of ADP. Occurrence of complexes I to V is highly conserved in eukaryotes, with exceptions being restricted to unicellular parasites that take up energy-rich compounds from their hosts...
April 27, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29731304/absence-of-complex-i-is-associated-with-diminished-respiratory-chain-function-in-european-mistletoe
#11
Andrew E Maclean, Alexander P Hertle, Joanna Ligas, Ralph Bock, Janneke Balk, Etienne H Meyer
Parasitism is a life history strategy found across all domains of life whereby nutrition is obtained from a host. It is often associated with reductive evolution of the genome, including loss of genes from the organellar genomes [1, 2]. In some unicellular parasites, the mitochondrial genome (mitogenome) has been lost entirely, with far-reaching consequences for the physiology of the organism [3, 4]. Recently, mitogenome sequences of several species of the hemiparasitic plant mistletoe (Viscum sp.) have been reported [5, 6], revealing a striking loss of genes not seen in any other multicellular eukaryotes...
April 26, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29729355/insertion-of-proteolipid-protein-into-mitochondria-but-not-dm20-regulates-metabolism-of-cells
#12
Mallika Somayajulu, Denise A Bessert, Maik Hüttemann, Jasloveleen Sohi, John Kamholz, Robert P Skoff
Proteolipid protein (PLP), besides its adhesive role in myelin, has been postulated to have multiple cellular functions. One well-documented function of PLP is regulation of oligodendrocyte (Olg) apoptosis. In contrast, DM20, an alternatively spliced product of the PLP1/Plp1 gene, has been proposed to have functions that are unique from PLP but these functions have never been elucidated. Here, we compare metabolism of PLP and DM20, and show that oxidative phosphorylation (OxPhos) was significantly decreased in Plp1 but not DM20 or EGFP expressing cells...
May 2, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29723585/platycodon-grandiflorum-derived-saponin-enhances-exercise-function-skeletal-muscle-protein-synthesis-and-mitochondrial-function
#13
Yong An Kim, Sun Woo Jin, Suck Hoon Oh, Gi Ho Lee, Hoa Thi Pham, Jae Ho Choi, Young Chul Chung, Wang Lok Lee, Sang Kyum Kim, Hye Gwang Jeong
Lower physical performance is an important risk factor in hypokinetic-related chronic disease, metabolic syndrome, and muscle atrophy. Our previous research demonstrated that Platycodon grandiflorum-derived saponin (PS) protects against eccentric exercise-induced muscle damage and mitochondrial function-related peroxisomal acyl-coenzme A oxidase (ACOX-1) and carnitine palmitoyltransferase (CPT-1) in high-fat diet-induced non-alcoholic steatohepatitis, and it inhibits osteoclast differentiation. However, the effects of PS on physical performance remain unknown...
April 30, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29718366/intratumoral-heterogeneity-of-oxygen-metabolism-and-neovascularization-uncovers-two-survival-relevant-subgroups-of-idh1-wild-type-glioblastoma
#14
Andreas Stadlbauer, Max Zimmermann, Arnd Doerfler, Stefan Oberndorfer, Michael Buchfelder, Roland Coras, Melitta Kitzwögerer, Karl Roessler
Background: The intratumoral heterogeneity of oxygen metabolism in combination with variable patterns of neovascularization (NV) as well as reprogramming of energy metabolism affects the landscape of tumor microenvironments (TMEs) in glioblastoma. Knowledge of the hypoxic and perivascular niches within the TME is essential for understanding treatment failure. Methods: Fifty-two patients with untreated glioblastoma (IDH1 wildtype) were examined with a physiological MRI protocol including a multiparametric quantitative blood-oxygen-level-dependent (qBOLD) approach and vascular architecture mapping (VAM)...
April 28, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29700325/kh176-safeguards-mitochondrial-diseased-cells-from-redox-stress-induced-cell-death-by-interacting-with-the-thioredoxin-system-peroxiredoxin-enzyme-machinery
#15
Julien Beyrath, Mina Pellegrini, Herma Renkema, Lisanne Houben, Svetlana Pecheritsyna, Peter van Zandvoort, Petra van den Broek, Akkiz Bekel, Pierre Eftekhari, Jan A M Smeitink
A deficient activity of one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzyme complexes leads to devastating diseases, with high unmet medical needs. Mitochondria, and more specifically the OXPHOS system, are the main cellular production sites of Reactive Oxygen Species (ROS). Increased ROS production, ultimately leading to irreversible oxidative damage of macromolecules or to more selective and reversible redox modulation of cell signalling, is a causative hallmark of mitochondrial diseases...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29700116/comparative-analysis-of-parkinson-s-disease-associated-genes-reveals-altered-survival-and-bioenergetics-of-parkin-deficient-dopamine-neurons-in-mice
#16
Nicolas Giguere, Consiglia Pacelli, Caroline Saumure, Marie-Josee Bourque, Diana Matheoud, Daniel Levesque, Ruth S Slack, David S Park, Louis-Eric Trudeau
Many mutations in genes encoding proteins such as parkin, PTEN-induced putative kinase 1 (PINK1), protein deglycase DJ-1 (DJ-1 or PARK7), leucine-rich repeat kinase 2 (LRRK2), and α-synuclein have been linked to familial forms of Parkinson's disease (PD). The consequences of these mutations, such as altered mitochondrial function and pathological protein aggregation, are starting to be better understood. However, little is known about the mechanisms explaining why alterations in such diverse cellular mechanisms lead to the selective loss of dopamine (DA) neurons in the substantia nigra (SNc) in the brain of individuals with PD...
April 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29698403/regulation-of-oxidative-phosphorylation-is-different-in-electrically-and-cortically-stimulated-skeletal-muscle
#17
Bernard Korzeniewski
A computer model of the skeletal muscle bioenergetic system was used to study the regulation of oxidative phosphorylation (OXPHOS) in electrically-stimulated and cortically-stimulated skeletal muscle. Two types of the dependence of the intensity of each-step activation (ESA) of OXPHOS complexes on ATP usage activity were tested: power-type dependence and saturating-type dependence. The dependence of muscle oxygen consumption ([Formula: see text]), phosphocreatine (PCr), cytosolic ADP, ATP, inorganic phosphate (Pi), pH and τp (characteristic transition time) of the principal component of the muscle [Formula: see text] on-kinetics on the ATP usage activity was simulated for both types of the ESA intensity-ATP usage activity dependence...
2018: PloS One
https://www.readbyqxmd.com/read/29691295/metformin-targets-mitochondrial-glycerophosphate-dehydrogenase-mgpdh-to-control-rate-of-oxidative-phosphorylation-and-growth-of-thyroid-cancer-in-vitro-and-in-vivo
#18
Shilpa Thakur, Brianna Daley, Kelli Gaskins, Vasyl V Vasko, Myriem Boufraqech, Dhaval Patel, Carole Sourbier, Jeff M Reece, Sheue-Yann Cheng, Electron Kebebew, Sunita K Agarwal, Joanna Klubo-Gwiezdzinska
PURPOSE: Mitochondrial glycerophosphate dehydrogenase (mGPDH) is the key enzyme connecting oxidative phosphorylation (OXPHOS) and glycolysis as well as a target of the antidiabetic drug metformin (MF) in the liver. There are no data on the expression and role of mGPDH as a metformin target in cancer. In this study, we evaluated mGPDH as a potential target of metformin in thyroid cancer and investigated its contribution in thyroid cancer metabolism. EXPERIMENTAL DESIGN: We analyzed mGPDH expression in 253 thyroid cancer and normal tissues by immunostaining and examined its expression and localization in thyroid cancer-derived cell lines (FTC133, BCPAP) by confocal microscopy...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29683527/modulation-of-allergic-responses-by-mitochondrial-stat3-inhibitors
#19
Tal Erlich, Israa Sharkia, Nadine Landolina, Miri Assayag, Omer Goldberger, Neville Berkman, Francesca Levi-Schafer, Ehud Razin
Recently we have shown that mast cell mitochondrial STAT3 could serve as a new target for the regulation of the allergic response as it plays an essential role in immunologically-mediated degranulation of mast cells. In the present work, we explored how two recently developed mitochondrial STAT3 inhibitors (Mitocur-1 and Mitocur-3) modulate the allergic response. Here we show that treatment of rodent and human cultured mast cells with low concentrations of mitochondrial STAT3 inhibitors had no effect on STAT3 target gene expression...
April 23, 2018: Allergy
https://www.readbyqxmd.com/read/29674655/reduced-oxidative-capacity-in-macrophages-results-in-systemic-insulin-resistance
#20
Saet-Byel Jung, Min Jeong Choi, Dongryeol Ryu, Hyon-Seung Yi, Seong Eun Lee, Joon Young Chang, Hyo Kyun Chung, Yong Kyung Kim, Seul Gi Kang, Ju Hee Lee, Koon Soon Kim, Hyun Jin Kim, Cuk-Seong Kim, Chul-Ho Lee, Robert W Williams, Hail Kim, Heung Kyu Lee, Johan Auwerx, Minho Shong
Oxidative functions of adipose tissue macrophages control the polarization of M1-like and M2-like phenotypes, but whether reduced macrophage oxidative function causes systemic insulin resistance in vivo is not clear. Here, we show that mice with reduced mitochondrial oxidative phosphorylation (OxPhos) due to myeloid-specific deletion of CR6-interacting factor 1 (Crif1), an essential mitoribosomal factor involved in biogenesis of OxPhos subunits, have M1-like polarization of macrophages and systemic insulin resistance with adipose inflammation...
April 19, 2018: Nature Communications
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