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NADH AND ATP

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https://www.readbyqxmd.com/read/28642839/the-mitochondrial-complex-i-ty-of-cancer
#1
REVIEW
Félix A Urra, Felipe Muñoz, Alenka Lovy, César Cárdenas
Recent evidence highlights that the cancer cell energy requirements vary greatly from normal cells and that cancer cells exhibit different metabolic phenotypes with variable participation of both glycolysis and oxidative phosphorylation. NADH-ubiquinone oxidoreductase (Complex I) is the largest complex of the mitochondrial electron transport chain and contributes about 40% of the proton motive force required for mitochondrial ATP synthesis. In addition, Complex I plays an essential role in biosynthesis and redox control during proliferation, resistance to cell death, and metastasis of cancer cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28631845/mild-metabolic-perturbations-alter-succinylation-of-mitochondrial-proteins
#2
Huanlian Chen, Hui Xu, Samuel Potash, Anatoly Starkov, Vsevolod V Belousov, Dmitry S Bilan, Travis T Denton, Gary E Gibson
Succinylation of proteins is widespread, modifies both the charge and size of the molecules, and can alter their function. For example, liver mitochondrial proteins have 1,190 unique succinylation sites representing multiple metabolic pathways. Succinylation is sensitive to both increases and decreases of the NAD(+) -dependent desuccinylase, SIRT5. Although the succinyl group for succinylation is derived from metabolism, the effects of systematic variation of metabolism on mitochondrial succinylation are not known...
June 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28615457/deconvoluting-amp-dependent-kinase-ampk-adenine-nucleotide-binding-and-sensing
#3
Xin Gu, Yan Yan, Scott J Novick, Amanda Kovich, Devrishi Goswami, Jiyuan Ke, M H Eileen Tan, Lili Wang, Xiaodan Li, Parker de Waal, Martin R Webb, Patrick R Griffin, H Eric Xu, Karsten Melcher
AMP-activated protein kinase (AMPK) is a central cellular energy sensor that adapts metabolism and growth to the energy state of the cell. AMPK senses the ratio of adenine nucleotides (adenylate energy charge) by competitive binding of AMP, ADP, and ATP to three sites (CBS1, CBS3, and CBS4) in its γ-subunit. Since these three binding sites are functionally interconnected, it remains unclear how nucleotides bind to individual sites, which nucleotides occupy each site under physiological conditions, and how binding to one site affects binding to the other sites...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28605655/aluminum-chloride-caused-liver-dysfunction-and-mitochondrial-energy-metabolism-disorder-in-rat
#4
Feibo Xu, Yanfen Liu, Hansong Zhao, Kaiyuan Yu, Miao Song, Yanzhu Zhu, Yanfei Li
Aluminum (Al) is known to exert hepatotoxicity. However, the mechanisms mostly are unclear. Liver is a metabolism organ that maintains the energy level and structural stability of body, mitochondria are the main sites of energy metabolism, thus, we hypothesized that mitochondrial energy metabolism disorder contributes to liver dysfunction in aluminum chloride (AlCl3) treatment rat. To verify the hypothesis, forty male Wistar rats were randomly allocated and orally exposed to 0, 64mg/kg, 128mg/kg and 256mg/kg body weight AlCl3 in drinking water for 120days, respectively...
April 20, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28601083/disruption-of-functional-activity-of-mitochondria-during-mtt-assay-of-viability-of-cultured-neurons
#5
A M Surin, R R Sharipov, I A Krasil'nikova, D P Boyarkin, O Yu Lisina, L R Gorbacheva, A V Avetisyan, V G Pinelis
The MTT assay based on the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium in the cell cytoplasm to a strongly light absorbing formazan is among the most commonly used methods for determination of cell viability and activity of NAD-dependent oxidoreductases. In the present study, the effects of MTT (0.1 mg/ml) on mitochondrial potential (ΔΨm), intracellular NADH, and respiration of cultured rat cerebellum neurons and isolated rat liver mitochondria were investigated. MTT caused rapid quenching of NADH autofluorescence, fluorescence of MitoTracker Green (MTG) and ΔΨm-sensitive probes Rh123 (rhodamine 123) and TMRM (tetramethylrhodamine methyl ester)...
June 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28582861/post-translational-oxidative-modifications-of-mitochondrial-complex-i-nadh-ubiquinone-oxidoreductase-implications-for-pathogenesis-and-therapeutics-in-human-diseases
#6
M M Srinivas Bharath
Mitochondrial complex I (NADH: ubiquinone oxidoreductase; CI) is central to the electron transfer chain (ETC), oxidative phosphorylation, and ATP production in eukaryotes. CI is a multi-subunit complex with a complicated yet organized structure that optimally connects electron transfer with proton translocation and forms higher-order supercomplexes with other ETC complexes. Efforts to understand the molecular genetics, expression profile of subunits, and structure-function relationship of CI have increased over the years due to the direct role of the complex in human diseases...
May 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28580284/nnt-reverse-mode-of-operation-mediates-glucose-control-of-mitochondrial-nadph-and-glutathione-redox-state-in-mouse-pancreatic-%C3%AE-cells
#7
Laila R B Santos, Carole Muller, Arnaldo H de Souza, Hilton K Takahashi, Peter Spégel, Ian R Sweet, Heeyoung Chae, Hindrik Mulder, Jean-Christophe Jonas
OBJECTIVE: The glucose stimulation of insulin secretion (GSIS) by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT) typically produces NADPH at the expense of NADH and ΔpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca(2+) influx, and GSIS, thereby leading to glucose intolerance. Here, we tested the role of NNT in the glucose regulation of mitochondrial NADPH and glutathione redox state and reinvestigated its role in GSIS coupling events in mouse pancreatic islets...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28553620/comparative-genomics-of-mycoplasma-bovis-strains-reveals-that-decreased-virulence-with-increasing-passages-might-correlate-with-potential-virulence-related-factors
#8
Muhammad A Rasheed, Jingjing Qi, Xifang Zhu, He Chenfei, Harish Menghwar, Farhan A Khan, Gang Zhao, Muhammad Zubair, Changmin Hu, Yingyu Chen, Huanchun Chen, Aizhen Guo
Mycoplasma bovis is an important cause of bovine respiratory disease worldwide. To understand its virulence mechanisms, we sequenced three attenuated M. bovis strains, P115, P150, and P180, which were passaged in vitro 115, 150, and 180 times, respectively, and exhibited progressively decreasing virulence. Comparative genomics was performed among the wild-type M. bovis HB0801 (P1) strain and the P115, P150, and P180 strains, and one 14.2-kb deleted region covering 14 genes was detected in the passaged strains...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28512016/mechanism-of-action-of-amp-jsa9-a-li-f-type-antimicrobial-peptide-produced-by-paenibacillus-polymyxa-jsa-9-against-fusarium-moniliforme
#9
Jinzhi Han, Fang Wang, Peng Gao, Zhi Ma, Shengming Zhao, Zhaoxin Lu, Fengxia Lv, Xiaomei Bie
LI-F type peptides (AMP-jsa9) are a group of cyclic lipodepsipeptides that exhibit broad antimicrobial spectrum against Gram-positive bacteria and filamentous fungi. We sought to assess the toxicity of AMP-jsa9 and the mechanism of AMP-jsa9 action against Fusarium moniliforme. AMP-jsa9 exhibited weak hemolytic activity and weak cytotoxicity at antimicrobial concentrations (32μg/ml). Confocal laser microscopy, SEM, and TEM indicated that AMP-jsa9 primarily targets the cell wall, plasma membrane, and cytoskeleton, increases membranepermeability, and enhances cytoplasm leakage (e...
May 13, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28503408/trifluoperazine-inhibits-acetaminophen-induced-hepatotoxicity-and-hepatic-reactive-nitrogen-formation-in-mice-and-in-freshly-isolated-hepatocytes
#10
Sudip Banerjee, Stepan B Melnyk, Kimberly J Krager, Nukhet Aykin-Burns, Sandra S McCullough, Laura P James, Jack A Hinson
The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocytes the nNOS (NOS1) inhibitor NANT inhibited APAP toxicity, reactive nitrogen and oxygen species formation, and mitochondrial dysfunction...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28472892/type-ii-nadh-dehydrogenase-ndh-2-a-promising-therapeutic-target-for-antitubercular-and-antibacterial-drug-discovery
#11
REVIEW
Satheeshkumar Sellamuthu, Meenakshi Singh, Ashok Kumar, Sushil Kumar Singh
Tuberculosis (TB) is highly dangerous due to the development of resistance to first-line drugs. Moreover, Mycobacterium tuberculosis (Mtb) has also developed resistance to newly approved antitubercular drug bedaquiline. This necessitates the search for drugs acting on newer molecular targets. The energy metabolism of mycobacteria is the prime focus for the discovery of novel antitubercular drugs. Targeting type-2 NADH dehydrogenase (NDH-2) involved in the production of respiratory ATP could, therefore, be effective in treating the disease...
June 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28461090/nad-dependent-deacetylase-sirtuin-5-rescues-the-innate-inflammatory-response-of-endotoxin-tolerant-macrophages-by-promoting-acetylation-of-p65
#12
Kewei Qin, Chaofeng Han, Hua Zhang, Tianliang Li, Nan Li, Xuetao Cao
The induction and persistence of a hypo-inflammatory and immunosuppressive state in severe sepsis is commonly associated with increased risks of secondary infections and mortality. Toll-like receptor (TLR)-triggered inflammatory response of macrophages/monocytes plays an important role in determining the outcome of hyper-inflammation during the acute phase and the hypo-inflammation during immunosuppressive phase of sepsis. However, the mechanisms for controlling hypo-inflammatory response in endotoxin tolerant macrophages remain to be fully understood...
July 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28450002/energy-status-regulates-disease-development-and-respiratory-metabolism-of-lasiodiplodia-theobromae-pat-griff-maubl-infected-longan-fruit
#13
Shen Zhang, Hetong Lin, Yifen Lin, Yixiong Lin, Yen-Con Hung, Yihui Chen, Hui Wang, John Shi
Lasiodiplodia theobromae (Pat.) Griff. & Maubl. is a major pathogen causing decay of harvested longan fruit. The roles of energy status regulated by 2,4-dinitrophenol (DNP) and adenosine triphosphate (ATP) in disease development regarding respiratory metabolism of L. theobromae-inoculated "Fuyan" longan fruit were studied. Compared with L. theobromae-inoculated longans, DNP treatment could promote the index of fruit disease, accelerate the decrease in energy charge, increase respiration rate and the activities of respiratory terminal oxidases like CCO, AAO and PPO, elevate contents of NAD and NADH, but decrease NAD kinase activity, as well as contents of NADP and NADPH; however, exogenous ATP supply acted contrarily...
September 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28429857/ndufa4l2-protects-against-ischemia-reperfusion-induced-cardiomyocyte-apoptosis-and-mitochondrial-dysfunction-by-inhibiting-complex-i
#14
Jianhua Li, Caiyan Bai, Junxia Guo, Wanqian Liang, Jingning Long
Myocardial ischemia/reperfusion (I/R) injury may cause the apoptosis of cardiomyocytes as well as mitochondrial dysfunction. The aims of the present study were to investigate whether NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) on myocardial ischemia-reperfusion (I/R) injury and the underlying molecular mechanism. The hypoxia-reperfusion (H/R) model was established in vitro using H9c2 cells to simulate I/R injury. NDUFA4L2 and complex I expression levels were detected using RT-PCR and western blot...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28404787/novel-atp-synthase-independent-mechanism-coupling-mitochondrial-activation-to-exocytosis-in-insulin-secreting-cells
#15
Umberto De Marchi, Aurelie Hermant, Jonathan Thevenet, Yann Ratinaud, Jaime Santo-Domingo, Denis Barron, Andreas Wiederkehr
Pancreatic beta-cells sense glucose promoting insulin secretion. Glucose sensing requires the sequential stimulation of glycolysis, mitochondrial metabolism and Ca(2+) entry. To elucidate how mitochondrial activation in beta-cells contributes to insulin secretion, we have compared the effects of glucose and the mitochondrial substrate methylsuccinate in INS-1E insulin secreting cells, at the respective concentrations they maximally activate mitochondrial respiration. Both substrates induced insulin secretion with distinct respiratory profiles, mitochondrial hyperpolarization, NADH production and ATP/ADP ratios...
April 12, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28403947/berberine-induced-bioactive-metabolites-of-the-gut-microbiota-improve-energy-metabolism
#16
Yan Wang, Jia-Wen Shou, Xiao-Yang Li, Zhen-Xiong Zhao, Jie Fu, Chi-Yu He, Ru Feng, Chao Ma, Bao-Ying Wen, Fang Guo, Xin-Yi Yang, Yan-Xing Han, Lu-Lu Wang, Qian Tong, Xue-Fu You, Yuan Lin, Wei-Jia Kong, Shu-Yi Si, Jian-Dong Jiang
OBJECTIVE: Berberine (BBR) clinically lowers blood lipid and glucose levels via multi-target mechanisms. One of the possible mechanisms is related to its effect on the short chain fatty acids (SCFAs) of the gut microbiota. The goal of this study is to investigate the therapeutic effect and mode of action of BBR working through SCFAs of the gut microbiota (especially, butyrate). METHODS: Gas chromatography (GC) was used to detect butyrate and other SCFAs chemically...
May 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28399854/improved-n-butanol-production-via-co-expression-of-membrane-targeted-tilapia-metallothionein-and-the-clostridial-metabolic-pathway-in-escherichia-coli
#17
Wei-Chih Chin, Kuo-Hsing Lin, Chun-Chi Liu, Kenji Tsuge, Chieh-Chen Huang
BACKGROUND: N-Butanol has favorable characteristics for use as either an alternative fuel or platform chemical. Bio-based n-butanol production using microbes is an emerging technology that requires further development. Although bio-industrial microbes such as Escherichia coli have been engineered to produce n-butanol, reactive oxygen species (ROS)-mediated toxicity may limit productivity. Previously, we show that outer-membrane-targeted tilapia metallothionein (OmpC-TMT) is more effective as an ROS scavenger than human and mouse metallothioneins to reduce oxidative stress in the host cell...
April 11, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28387366/elucidating-dynamic-metabolic-physiology-through-network-integration-of-quantitative-time-course-metabolomics
#18
Aarash Bordbar, James T Yurkovich, Giuseppe Paglia, Ottar Rolfsson, Ólafur E Sigurjónsson, Bernhard O Palsson
The increasing availability of metabolomics data necessitates novel methods for deeper data analysis and interpretation. We present a flux balance analysis method that allows for the computation of dynamic intracellular metabolic changes at the cellular scale through integration of time-course absolute quantitative metabolomics. This approach, termed "unsteady-state flux balance analysis" (uFBA), is applied to four cellular systems: three dynamic and one steady-state as a negative control. uFBA and FBA predictions are contrasted, and uFBA is found to be more accurate in predicting dynamic metabolic flux states for red blood cells, platelets, and Saccharomyces cerevisiae...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385814/tnf%C3%AE-enhances-force-generation-in-airway-smooth-muscle
#19
Murat Dogan, Young-Soo Han, Philippe Delmotte, Gary C Sieck
Airway inflammation is a hallmark of asthma, triggering airway smooth muscle (ASM) hyperreactivity and airway remodeling. TNFα increases both agonist-induced cytosolic Ca(2+) concentration ([Ca(2+)]cyt) and force in ASM. The effects of TNFα on ASM force may also be due to an increase in Ca(2+) sensitivity, cytoskeletal remodeling, and/or changes in contractile protein content. We hypothesized that 24 h of exposure to TNFα increases ASM force by changing actin and myosin heavy chain (MyHC) content and/or polymerization...
June 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28364805/transcriptomic-alterations-in-sitophilus-zeamais-in-response-to-allyl-isothiocyanate-fumigation
#20
Chao Zhang, Zhiqing Ma, Xing Zhang, Hua Wu
To study the fumigation mechanisms of Allyl isothiocyanate (AITC) a promising biorational alternative to present fumigants (phosphine and methyl bromide), and provide theoretical basis for its further development in the control of stored grain pests, this research presents a transcriptome analysis of Sitophilus zeamais fumigated with AITC at the concentration of LC50 (5.69μg/mL) and control over 8h. 21,869,022 and 23,873,110 clean reads in insects fumigated with AITC and control were gained, respectively. The results of RNA-seq were confirmed by qRT-PCR determination of the expression levels of NADH dehydrogenase subunit 6 and Vacuolar ATP synthase subunit B in the insects fumigated with AITC at different concentrations...
April 2017: Pesticide Biochemistry and Physiology
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