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Mitochondrial respiration

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https://www.readbyqxmd.com/read/28432298/endogenous-two-photon-excited-fluorescence-imaging-characterizes-neuron-and-astrocyte-metabolic-responses-to-manganese-toxicity
#1
Emily Stuntz, Yusi Gong, Disha Sood, Volha Liaudanskaya, Dimitra Pouli, Kyle P Quinn, Carlo Alonzo, Zhiyi Liu, David L Kaplan, Irene Georgakoudi
As neurodegenerative conditions are increasingly linked to mitochondrial dysfunction, methods for studying brain cell metabolism at high spatial resolution are needed to elucidate neurodegeneration mechanisms. Two-photon excited fluorescence (TPEF) imaging is a non-destructive, high-resolution technique for studying cell metabolism via endogenous fluorescence of reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD). We employed TPEF to study the metabolism of primary rat astrocyte and neuronal cultures under normal growth conditions and in response to manganese (Mn) treatment...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432125/sequential-adaptive-changes-in-a-c-myc-driven-model-of-hepatocellular-carcinoma
#2
James M Dolezal, Huabo Wang, Sucheta Kulkarni, Laura Jackson, Jie Lu, Sarangarajan Ranganathan, Eric S Goetzman, Sivakama Bharathi, Kevin Beezhold, Craig A Byersdorfer, Edward V Prochownik
Hepatocellular carcinoma (HCC) is a common cancer that frequently over-expresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied the metabolic, biochemical and molecular changes accompanying HCC progression, regression and recurrence. These involved altered rates of pyruvate and fatty acid β-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain Complexes I and II to respiration...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28429737/the-glutamate-cystine-xct-antiporter-antagonizes-glutamine-metabolism-and-reduces-nutrient-flexibility
#3
Chun-Shik Shin, Prashant Mishra, Jeramie D Watrous, Valerio Carelli, Marilena D'Aurelio, Mohit Jain, David C Chan
As noted by Warburg, many cancer cells depend on the consumption of glucose. We performed a genetic screen to identify factors responsible for glucose addiction and recovered the two subunits of the xCT antiporter (system xc(-)), which plays an antioxidant role by exporting glutamate for cystine. Disruption of the xCT antiporter greatly improves cell viability after glucose withdrawal, because conservation of glutamate enables cells to maintain mitochondrial respiration. In some breast cancer cells, xCT antiporter expression is upregulated through the antioxidant transcription factor Nrf2 and contributes to their requirement for glucose as a carbon source...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429368/-aralar-agc1-deficiency-a-neurodevelopmental-disorder-with-severe-impairment-of-neuronal-mitochondrial-respiration-does-not-produce-a-primary-increase-in-brain-lactate
#4
Inés Juaristi, María L García-Martin, Tiago B Rodrigues, Jorgina Satrústegui, Irene Llorente-Folch, Beatriz Pardo
ARALAR/AGC1 (aspartate-glutamate mitochondrial carrier 1) is an important component of the NADH malate-aspartate shuttle (MAS). AGC1-deficiency is a rare disease causing global cerebral hypomyelination, developmental arrest, hypotonia, and epilepsy (OMIM ID #612949); the aralar-KO mouse recapitulates the major findings in humans. This study was aimed at understanding the impact of ARALAR-deficiency in brain lactate levels as a biomarker. We report that lactate was equally abundant in wild-type and aralar-KO mouse brain in vivo at PND 17...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28428250/functional-roles-of-globin-proteins-in-hypoxia-tolerant-ectothermic-vertebrates
#5
Angela Fago
Globins are heme-containing proteins ubiquitously expressed in vertebrates, where they serve a broad range of biological functions, directly or indirectly related to the tight control of oxygen levels and its toxic products in vivo. Perhaps the most investigated of all proteins, hemoglobin and myoglobin are primarily involved in oxygen transport and storage, but also in facilitating arterial vasodilation, suppressing mitochondrial respiration and preventing tissue oxidative damage via accessory redox enzymatic activities during hypoxia...
April 20, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28428045/sco2-deficient-mice-develop-increased-adiposity-and-insulin-resistance
#6
Shauna Hill, Sathyaseelan S Deepa, Kavithalakshmi Sataranatarajan, Pavithra Premkumar, Daniel Pulliam, Yuhong Liu, Vanessa Y Soto, Kathleen E Fischer, Holly Van Remmen
Cytochrome c oxidase (COX) is an essential transmembrane protein complex (Complex IV) in the mitochondrial respiratory electron chain. Mutations in genes responsible for the assembly of COX are associated with Leigh syndrome, cardiomyopathy, spinal muscular atrophy and other fatal metabolic disorders in humans. Previous studies have shown that mice lacking the COX assembly protein Surf1 (Surf1(-/-) mice) paradoxically show a number of beneficial metabolic phenotypes including increased insulin sensitivity, upregulation of mitochondrial biogenesis, induction of stress response pathways and increased lifespan...
April 17, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28427446/respiratory-chain-complex-iii-deficiency-due-to-mutated-bcs1l-a-novel-phenotype-with-encephalomyopathy-partially-phenocopied-in-a-bcs1l-mutant-mouse-model
#7
Saara Tegelberg, Nikica Tomašić, Jukka Kallijärvi, Janne Purhonen, Eskil Elmér, Eva Lindberg, David Gisselsson Nord, Maria Soller, Nicole Lesko, Anna Wedell, Helene Bruhn, Christoph Freyer, Henrik Stranneheim, Rolf Wibom, Inger Nennesmo, Anna Wredenberg, Erik A Eklund, Vineta Fellman
BACKGROUND: Mitochondrial diseases due to defective respiratory chain complex III (CIII) are relatively uncommon. The assembly of the eleven-subunit CIII is completed by the insertion of the Rieske iron-sulfur protein, a process for which BCS1L protein is indispensable. Mutations in the BCS1L gene constitute the most common diagnosed cause of CIII deficiency, and the phenotypic spectrum arising from mutations in this gene is wide. RESULTS: A case of CIII deficiency was investigated in depth to assess respiratory chain function and assembly, and brain, skeletal muscle and liver histology...
April 20, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28427248/caloric-restriction-induced-extension-of-chronological-lifespan-requires-intact-respiration-in-budding-yeast
#8
Young-Yon Kwon, Sung-Keun Lee, Cheol-Koo Lee
Caloric restriction (CR) has been shown to extend lifespan and prevent cellular senescence in various species ranging from yeast to humans. Many effects of CR may contribute to extend lifespan. Specifically, CR prevents oxidative damage from reactive oxygen species (ROS) by enhancing mitochondrial function. In this study, we characterized 33 single electron transport chain (ETC) gene-deletion strains to identify CR-induced chronological lifespan (CLS) extension mechanisms. Interestingly, defects in 17 of these 33 ETC genedeleted strains showed loss of both respiratory function and CR-induced CLS extension...
April 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28425440/the-valosin-containing-protein-is-a-novel-mediator-of-mitochondrial-respiration-and-cell-survival-in-the-heart-in-vivo
#9
Paulo Lizano, Eman Rashed, Shaunrick Stoll, Ning Zhou, Hairuo Wen, Tristan T Hays, Gangjian Qin, Lai-Hua Xie, Christophe Depre, Hongyu Qiu
The valosin-containing protein (VCP) participates in signaling pathways essential for cell homeostasis in multiple tissues, however, its function in the heart in vivo remains unknown. Here we offer the first description of the expression, function and mechanism of action of VCP in the mammalian heart in vivo in both normal and stress conditions. By using a transgenic (TG) mouse with cardiac-specific overexpression (3.5-fold) of VCP, we demonstrate that VCP is a new and powerful mediator of cardiac protection against cell death in vivo, as evidenced by a 50% reduction of infarct size after ischemia/reperfusion versus wild type...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424712/a-functional-approach-towards-understanding-the-role-of-the-mitochondrial-respiratory-chain-in-an-endomycorrhizal-symbiosis
#10
Louis Mercy, Eva Lucic-Mercy, Amaia Nogales, Areg Poghosyan, Carolin Schneider, Birgit Arnholdt-Schmitt
Arbuscular mycorrhizal fungi (AMF) are crucial components of fertile soils, able to provide several ecosystem services for crop production. Current economic, social and legislative contexts should drive the so-called "second green revolution" by better exploiting these beneficial microorganisms. Many challenges still need to be overcome to better understand the mycorrhizal symbiosis, among which (i) the biotrophic nature of AMF, constraining their production, while (ii) phosphate acts as a limiting factor for the optimal mycorrhizal inoculum application and effectiveness...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28424622/pravastatin-chronic-treatment-sensitizes-hypercholesterolemic-mice-muscle-to-mitochondrial-permeability-transition-protection-by-creatine-or-coenzyme-q10
#11
Estela N B Busanello, Ana C Marques, Noelia Lander, Diogo N de Oliveira, Rodrigo R Catharino, Helena C F Oliveira, Anibal E Vercesi
Statins are efficient cholesterol-lowering medicines utilized worldwide. However, 10% of patients suffer from adverse effects specially related to skeletal muscle function. Pro- or anti-oxidant effects of statins have been reported. Here we hypothesized that statins induce muscle mitochondrial oxidative stress leading to mitochondrial permeability transition (MPT) which may explain statin muscle toxicity. Thus, our aims were to investigate the effects of statin chronic treatment on muscle mitochondrial respiration rates, MPT and redox state indicators in the context of hypercholesterolemia...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28423196/melatonin-enhances-neural-stem-cell-differentiation-and-engraftment-by-increasing-mitochondrial-function
#12
Miguel Mendivil-Perez, Viviana Soto-Mercado, Ana Guerra-Librero, Beatriz I Fernandez-Gil, Javier Florido, Ying-Qiang Shen, Miguel A Tejada, Vivian Capilla-Gonzalez, Iryna Rusanova, José M Garcia-Verdugo, Darío Acuña-Castroviejo, Luis Carlos López, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio, José M Ferrer, Germaine Escames
Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established...
April 19, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28417920/evaluation-of-the-potential-risk-of-drugs-to-induce-hepatotoxicity-in-human-relationships-between-hepatic-steatosis-observed-in-non-clinical-toxicity-study-and-hepatotoxicity-in-humans
#13
Keisuke Goda, Akio Kobayashi, Akemi Takahashi, Tadakazu Takahashi, Kosuke Saito, Keiko Maekawa, Yoshiro Saito, Shoichiro Sugai
In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury (DILI) in humans...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28417315/disruption-of-energy-transfer-and-redox-status-by-sulfite-in-hippocampus-striatum-and-cerebellum-of-developing-rats
#14
Leonardo de Moura Alvorcem, Mateus Struecker da Rosa, Nícolas Manzke Glänzel, Belisa Parmeggiani, Mateus Grings, Felipe Schmitz, Angela T S Wyse, Moacir Wajner, Guilhian Leipnitz
Patients with sulfite oxidase (SO) deficiency present severe brain abnormalities, whose pathophysiology is not yet elucidated. We evaluated the effects of sulfite and thiosulfate, metabolites accumulated in SO deficiency, on creatine kinase (CK) activity, mitochondrial respiration and redox status in hippocampus, striatum and cerebellum of developing rats. Our in vitro results showed that sulfite and thiosulfate decreased CK activity, whereas sulfite also increased malondialdehyde (MDA) levels in all brain structures evaluated...
April 17, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28416581/trp-channels-in-brown-and-white-adipogenesis-from-human-progenitors-new-therapeutic-targets-and-the-caveats-associated-with-the-common-antibiotic-streptomycin
#15
Anna Goralczyk, Marc van Vijven, Mathilde Koch, Cedric Badowski, M Shabeer Yassin, Sue-Anne Toh, Asim Shabbir, Alfredo Franco-Obregón, Michael Raghunath
Transient receptor potential (TRP) channels are polymodal cell sensors responding to diverse stimuli and widely implicated in the developmental programs of numerous tissues. The evidence for an involvement of TRP family members in adipogenesis, however, is scant. We present the first comprehensive expression profile of all known 27 human TRP genes in mesenchymal progenitors cells during white or brown adipogenesis. Using positive trilineage differentiation as an exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to be uniquely adipospecific...
April 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28415782/glutaminase-inhibitor-cb-839-synergizes-with-carfilzomib-in-resistant-multiple-myeloma-cells
#16
Ravyn M Thompson, Dominik Dytfeld, Leticia Reyes, Reeder M Robinson, Brittany Smith, Yefim Manevich, Andrzej Jakubowiak, Mieczyslaw Komarnicki, Anna Przybylowicz-Chalecka, Tomasz Szczepaniak, Amit K Mitra, Brian G Van Ness, Magdalena Luczak, Nathan G Dolloff
Curative responses in the treatment of multiple myeloma (MM) are limited by the emergence of therapeutic resistance. To address this problem, we set out to identify druggable mechanisms that convey resistance to proteasome inhibitors (PIs; e.g., bortezomib), which are cornerstone agents in the treatment of MM. In isogenic pairs of PI sensitive and resistant cells, we observed stark differences in cellular bioenergetics between the divergent phenotypes. PI resistant cells exhibited increased mitochondrial respiration driven by glutamine as the principle fuel source...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414908/an-experimental-computational-study-of-carbon-nanotubes-effects-on-mitochondrial-respiration-in-silico-nano-qspr-machine-learning-models-based-on-new-raman-spectra-transform-with-markov-shannon-entropy-invariants
#17
Michael González-Durruthy, Luciane Carla Alberici, Zeki Naal, David T Atique-Sawazaki, Carlos Curti, José Manuel Vázquez-Naya, Humbert Gonzalez-Diaz, Cristian Robert Munteanu
The study of selective toxicity of carbon nanotubes (CNT) on mitochondria (CNT-mitotoxicity) is of major interest for future biomedical applications. In the current work, the mitochondrial oxygen consumption (E3) is measured under three experimental conditions by exposure to pristine and oxidized CNTs (hydroxylated and carboxylated). Respiratory functional assays showed that the information of the CNT-Raman spectroscopy could be useful to predict structural parameters of mitotoxicity induced by CNTs. The in vitro functional assays show that the mitochondrial oxidative phosphorylation by ATP-synthase (or state V3 of respiration) was not perturbed in isolated rat-liver mitochondria...
April 17, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28414727/trypanosoma-brucei-tbif1-inhibits-the-essential-f1-atpase-in-the-infectious-form-of-the-parasite
#18
Brian Panicucci, Ondřej Gahura, Alena Zíková
The mitochondrial (mt) FoF1-ATP synthase of the digenetic parasite, Trypanosoma brucei, generates ATP during the insect procyclic form (PF), but becomes a perpetual consumer of ATP in the mammalian bloodstream form (BF), which lacks a canonical respiratory chain. This unconventional dependence on FoF1-ATPase is required to maintain the essential mt membrane potential (Δψm). Normally, ATP hydrolysis by this rotary molecular motor is restricted to when eukaryotic cells experience sporadic hypoxic conditions, during which this compulsory function quickly depletes the cellular ATP pool...
April 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28412346/superoxide-is-the-critical-driver-of-dopal-autoxidation-lysyl-adduct-formation-and-crosslinking-of-%C3%AE-synuclein
#19
Jon W Werner-Allen, Rodney L Levine, Ad Bax
Parkinson's disease has long been associated with redox imbalance and oxidative stress in dopaminergic neurons. The catecholaldehyde hypothesis proposes that 3,4-dihydroxyphenylacetaldehyde (DOPAL), an obligate product of dopamine catabolism, is a central nexus in a network of pathways leading to disease-state neurodegeneration, owing to its toxicity and potent ability to oligomerize α-synuclein, the main component of protein aggregates in Lewy bodies. In this work we examine the connection between reactive oxygen species and DOPAL autoxidation...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28409855/the-mobility-of-mitochondria-intercellular-trafficking-in-health-and-disease
#20
Michael V Berridge, Jiri Neuzil
The view that genes are constrained within somatic cells is challenged by in vitro evidence, and more recently by in vivo studies which demonstrate that mitochondria with their mitochondrial DNA (mtDNA) payload not only can, but do move between cells in tumour models and in mouse models of tissue damage. Using mouse tumour cell models without mtDNA to reflect mtDNA damage, we have shown that these cells grow tumours only after acquiring mtDNA from cells in the local microenvironment resulting in respiration recovery, tumorigenesis and metastasis...
April 13, 2017: Clinical and Experimental Pharmacology & Physiology
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