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NADH AND ATP

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https://www.readbyqxmd.com/read/27912063/structure-of-mammalian-respiratory-supercomplex-i1iii2iv1
#1
Meng Wu, Jinke Gu, Runyu Guo, Yushen Huang, Maojun Yang
The mammalian respiratory chain complexes assemble into supercomplexes (SCs) and reside in the inner mitochondrial membrane to transfer electrons and establish the proton gradient for complex V to synthesize ATP. The precise arrangement of SCs is largely unknown. Here, we report a 4.0-Å cryo-electron microscopy (cryo-EM) structure of the major SC in porcine heart, the 1.7-MDa SCI1III2IV1. The complex III (CIII) dimer and complex IV (CIV) bind at the same side of the L-shaped complex I (CI). Several accessory or supernumerary subunits of CI, such as NDUFA11, NDUFB4, NDUFB8, and NDUFB9, directly contribute to the oligomerization of CI, CIII, and CIV...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27896650/neuroprotection-by-chlorpromazine-and-promethazine-in-severe-transient-and-permanent-ischemic-stroke
#2
Xiaokun Geng, Fengwu Li, James Yip, Changya Peng, Omar Elmadhoun, Jiamei Shen, Xunming Ji, Yuchuan Ding
Previous studies have demonstrated depressive or hibernation-like roles of phenothiazine neuroleptics [combined chlorpromazine and promethazine (C + P)] in brain activity. This ischemic stroke study aimed to establish neuroprotection by reducing oxidative stress and improving brain metabolism with post-ischemic C + P administration. Sprague-Dawley rats were subjected to transient (2 or 4 h) middle cerebral artery occlusion (MCAO) followed by 6 or 24 h reperfusion, or permanent (28 h) MCAO without reperfusion...
November 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27896382/the-mechanism-of-improved-intracellular-organic-selenium-and-glutathione-contents-in-selenium-enriched-candida-utilis-by-acid-stress
#3
Gao-Chuan Zhang, Da-Hui Wang, Dong-Hua Wang, Gong-Yuan Wei
Batch culture of Candida utilis CCTCC M 209298 for the preparation of selenium (Se)-enriched yeast was carried out under different pH conditions, and maximal intracellular organic Se and glutathione (GSH) contents were obtained in a moderate acid stress environment (pH 3.5). In order to elucidate the physiological mechanism of improved performance of Se-enriched yeast by acid stress, assays of the key enzymes involved in GSH biosynthesis and determinations of energy supply and regeneration were performed. The results indicated that moderate acid stress increased the activity of γ-glutamylcysteine synthetase and the ratios of NADH/NAD(+) and ATP/ADP, although no significant changes in intracellular pH were observed...
November 28, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27886975/in-vitro-metabolic-engineering-of-bioelectricity-generation-by-the-complete-oxidation-of-glucose
#4
Zhiguang Zhu, Y-H Percival Zhang
The direct generation of electricity from the most abundant renewable sugar, glucose, is an appealing alternative to the production of liquid biofuels and biohydrogen. However, enzyme-catalyzed bioelectricity generation from glucose suffers from low yields due to the incomplete oxidation of the six-carbon compound glucose via one or few enzymes. Here, we demonstrate a synthetic ATP- and CoA-free 12-enzyme pathway to implement the complete oxidation of glucose in vitro. This pathway is comprised of glucose phosphorylation via polyphosphate glucokinase, NADH generation catalyzed by glucose 6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH), electron transfer from NADH to the anode, and glucose 6-phosphate regeneration via the non-oxidative pentose phosphate pathway and gluconeogenesis...
November 23, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27886267/in-vivo-characterization-of-hair-and-skin-derived-carbon-quantum-dots-with-high-quantum-yield-as-long-term-bioprobes-in-zebrafish
#5
Jing-Hui Zhang, Aping Niu, Jing Li, Jian-Wei Fu, Qun Xu, De-Sheng Pei
Carbon quantum dots (CDs) were widely investigated because of their tunable fluorescence properties and low toxicity. However, so far there have been no reports on in vivo functional studies of hair and skin derived CDs. Here, hair derived CDs (HCDs) and skin derived CDs (SCDs) were produced by using human hair and pig skin as precursors. The quantum yields (QYs) of HCDs and SCDs were quite high, compared to citric acid derived CDs (CCDs). HCDs and SCDs possess optimal photostability, hypotoxicity and biocompatibility in zebrafish, indicating that HCDs and SCDs possess the capacity of being used as fluorescence probes for in vivo biological imaging...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27885254/aldehyde-dehydrogenase-is-used-by-cancer-cells-for-energy-metabolism
#6
Joon Hee Kang, Seon-Hyeong Lee, Dongwan Hong, Jae-Seon Lee, Hee-Sung Ahn, Ju-Hyun Ahn, Tae Wha Seong, Chang-Hun Lee, Hyonchol Jang, Kyeong Man Hong, Cheolju Lee, Jae-Ho Lee, Soo-Youl Kim
We found that non-small-cell lung cancer (NSCLC) cells express high levels of multiple aldehyde dehydrogenase (ALDH) isoforms via an informatics analysis of metabolic enzymes in NSCLC and immunohistochemical staining of NSCLC clinical tumor samples. Using a multiple reaction-monitoring mass spectrometry analysis, we found that multiple ALDH isozymes were generally abundant in NSCLC cells compared with their levels in normal IMR-90 human lung cells. As a result of the catalytic reaction mediated by ALDH, NADH is produced as a by-product from the conversion of aldehyde to carboxylic acid...
November 25, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27845672/gpu-based-point-cloud-superpositioning-for-structural-comparisons-of-protein-binding-sites
#7
Matthias Leinweber, Thomas Fober, Bernd Freisleben
In this paper, we present a novel approach to solve the labeled point cloud superpositioning problem for performing structural comparisons of protein binding sites. The solution is based on a parallel evolution strategy that operates on large populations and runs on GPU hardware. The proposed evolution strategy reduces the likelihood of getting stuck in a local optimum of the multimodal real-valued optimization problem represented by labeled point cloud superpositioning. The performance of the GPU-based parallel evolution strategy is compared to a previously proposed CPU-based sequential approach for labeled point cloud superpositioning, indicating that the GPU-based parallel evolution strategy leads to qualitatively better results and significantly shorter runtimes, with speed improvements of up to a factor of 1,500 for large populations...
November 7, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/27815040/the-addition-of-ketone-bodies-alleviates-mitochondrial-dysfunction-by-restoring-complex-i-assembly-in-a-melas-cellular-model
#8
Samuel Frey, Guillaume Geffroy, Valerie Desquiret-Dumas, Naig Gueguen, Celine Bris, Sophie Belal, Patrizia Amati-Bonneau, Arnaud Chevrollier, Magalie Barth, Daniel Henrion, Guy Lenaers, Dominique Bonneau, Pascal Reynier, Vincent Procaccio
Ketogenic Diet used to treat refractory epilepsy for almost a century may represent a treatment option for mitochondrial disorders for which effective treatments are still lacking. Mitochondrial complex I deficiencies are involved in a broad spectrum of inherited diseases including Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes syndrome leading to recurrent cerebral insults resembling strokes and associated with a severe complex I deficiency caused by mitochondrial DNA (mtDNA) mutations...
November 1, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27812026/identification-of-g8969-a-in-mitochondrial-atp6-gene-that-severely-compromises-atp-synthase-function-in-a-patient-with-iga-nephropathy
#9
Shuzhen Wen, Katarzyna Niedzwiecka, Weiwei Zhao, Shutian Xu, Shaoshan Liang, Xiaodong Zhu, Honglang Xie, Déborah Tribouillard-Tanvier, Marie-France Giraud, Caihong Zeng, Alain Dautant, Róża Kucharczyk, Zhihong Liu, Jean-Paul di Rago, Huimei Chen
Here we elucidated the pathogenesis of a 14-year-old Chinese female who initially developed an isolated nephropathy followed by a complex clinical presentation with brain and muscle problems, which indicated that the disease process was possibly due to a mitochondrial dysfunction. Careful evaluation of renal biopsy samples revealed a decreased staining of cells induced by COX and NADH dehydrogenase activities, and a strong fragmentation of the mitochondrial network. These anomalies were due to the presence of a mutation in the mitochondrial ATP6 gene, G8969>A...
November 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799279/non-canonical-transcription-initiation-the-expanding-universe-of-transcription-initiating-substrates
#10
REVIEW
Ivan Barvík, Dominik Rejman, Natalya Panova, Hana Šanderová, Libor Krásný
RNA polymerase (RNAP) is the central enzyme of transcription of the genetic information from DNA into RNA. RNAP recognizes four main substrates: ATP, CTP, GTP and UTP. Experimental evidence from the past several years suggests that, besides these four NTPs, other molecules can be used to initiate transcription: (i) ribooligonucleotides (nanoRNAs) and (ii) coenzymes such as NAD(+), NADH, dephospho-CoA and FAD. The presence of these molecules at the 5' ends of RNAs affects the properties of the RNA. Here, we discuss the expanding portfolio of molecules that can initiate transcription, their mechanism of incorporation, effects on RNA and cellular processes, and we present an outlook toward other possible initiation substrates...
October 30, 2016: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/27793977/acute-stimulation-of-glucose-influx-upon-mitoenergetic-dysfunction-requires-lkb1-ampk-sirt2-and-mtor-raptor
#11
Dania C Liemburg-Apers, Jori A L Wagenaars, Jan A M Smeitink, Peter H G M Willems, Werner J H Koopman
Mitochondria play a central role in cellular energy production, and their dysfunction can trigger a compensatory increase in glycolytic flux to sustain cellular ATP levels. Here, we studied the mechanism of this homeostatic phenomenon in C2C12 myoblasts. Acute (30 min) mitoenergetic dysfunction induced by the mitochondrial inhibitors piericidin A and antimycin A stimulated Glut1-mediated glucose uptake without altering Glut1 (also known as SLC2A1) mRNA or plasma membrane levels. The serine/threonine liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK) played a central role in this stimulation...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27783701/decreased-integrity-content-and-increased-transcript-level-of-mitochondrial-dna-are-associated-with-keratoconus
#12
Xiao-Dan Hao, Zhao-Li Chen, Ming-Li Qu, Xiao-Wen Zhao, Su-Xia Li, Peng Chen
Oxidative stress may play an important role in the pathogenesis of keratoconus (KC). Mitochondrial DNA (mtDNA) is involved in mitochondrial function, and the mtDNA content, integrity, and transcript level may affect the generation of reactive oxygen species (ROS) and be involved in the pathogenesis of KC. We designed a case-control study to research the relationship between KC and mtDNA integrity, content and transcription. One-hundred ninety-eight KC corneas and 106 normal corneas from Chinese patients were studied...
2016: PloS One
https://www.readbyqxmd.com/read/27760881/impaired-cyclic-electron-flow-around-photosystem-i-disturbs-high-light-respiratory-metabolism
#13
Igor Florez-Sarasa, Ko Noguchi, Wagner L Araújo, Ana Garcia-Nogales, Alisdair R Fernie, Jaume Flexas, Miquel Ribas-Carbo
The cyclic electron flow around photosystem I (CEF-PSI) increases ATP/NADPH production in the chloroplast, acting as an energy balance mechanism. Higher export of reducing power from the chloroplast in CEF-PSI mutants has been correlated with higher mitochondrial alternative oxidase (AOX) capacity and protein amount under high-light (HL) conditions. However, in vivo measurements of AOX activity are still required to confirm the exact role of AOX in dissipating the excess of reductant power from the chloroplast...
December 2016: Plant Physiology
https://www.readbyqxmd.com/read/27739595/3-hydroxybutyrate-regulates-energy-metabolism-and-induces-bdnf-expression-in-cerebral-cortical-neurons
#14
Krisztina Marosi, Sang Woo Kim, Keelin Moehl, Morten Scheibye-Knudsen, Aiwu Cheng, Roy Cutler, Simonetta Camandola, Mark P Mattson
During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons maintained in the presence of 3OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD(+) /NADH ratio. We found that 3OHB metabolism increases mitochondrial respiration which drives changes in expression of brain-derived neurotrophic factor (BDNF) in cultured cerebral cortical neurons...
December 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27724820/increased-hippocampal-cd38-and-systemic-inflammation-after-partial-hepatectomy-does-not-induce-impairment-of-spatial-cognition
#15
Sebastian Schnitzler, Jürgen Kopitz, Konstanze Plaschke
OBJECTIVE: The role of inflammation in cognitive alterations in a post-operative setting is still not fully understood. Surgical interventions can cause systemic inflammations which eventually can induce neuroinflammation. However, the main causes of functional changes after surgery are still elusive. In this study, we investigated the role of CD38, a TNFα-inducible NADH(+) cyclase and hydrolase. We assume that CD38 overexpression impairs mitochondrial ATP synthesis. Within the hippocampus, the resulting cellular death could lead to cognitive impairment...
October 11, 2016: Neurological Research
https://www.readbyqxmd.com/read/27717801/nadh-dehydrogenase-of-trypanosoma-brucei-is-important-for-efficient-acetate-production-in-bloodstream-forms
#16
Sachin V Surve, Brian C Jensen, Meredith Heestand, Muriel Mazet, Terry K Smith, Frédéric Bringaud, Marilyn Parsons, Achim Schnaufer
In the slender bloodstream form, Trypanosoma brucei mitochondria are repressed for many functions. Multiple components of mitochondrial complex I, NADH:ubiquinone oxidoreductase, are expressed in this stage, but electron transfer through complex I is not essential. Here we investigate the role of the parasite's second NADH:ubiquinone oxidoreductase, NDH2, which is composed of a single subunit that also localizes to the mitochondrion. While inducible knockdown of NDH2 had a modest growth effect in bloodstream forms, NDH2 null mutants, as well as inducible knockdowns in a complex I deficient background, showed a greater reduction in growth...
October 4, 2016: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/27714559/caco3-supplementation-alleviates-the-inhibition-of-formic-acid-on-acetone-butanol-ethanol-fermentation-by-clostridium-acetobutylicum
#17
Gaoxiang Qi, Lian Xiong, Xiaoqing Lin, Chao Huang, Hailong Li, Xuefang Chen, Xinde Chen
OBJECTIVE: To investigate the inhibiting effect of formic acid on acetone/butanol/ethanol (ABE) fermentation and explain the mechanism of the alleviation in the inhibiting effect under CaCO3 supplementation condition. RESULTS: From the medium containing 50 g sugars l(-1) and 0.5 g formic acid l(-1), only 0.75 g ABE l(-1) was produced when pH was adjusted by KOH and fermentation ended prematurely before the transformation from acidogenesis to solventogenesis. In contrast, 11...
October 6, 2016: Biotechnology Letters
https://www.readbyqxmd.com/read/27706102/the-redox-status-of-cancer-cells-supports-mechanisms-behind-the-warburg-effect
#18
Jorgelindo da Veiga Moreira, Minoo Hamraz, Mohammad Abolhassani, Erwan Bigan, Sabine Pérès, Loïc Paulevé, Marcel Levy Nogueira, Jean-Marc Steyaert, Laurent Schwartz
To better understand the energetic status of proliferating cells, we have measured the intracellular pH (pHi) and concentrations of key metabolites, such as adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP) in normal and cancer cells, extracted from fresh human colon tissues. Cells were sorted by elutriation and segregated in different phases of the cell cycle (G0/G1/S/G2/M) in order to study their redox (NAD, NADP) and bioenergetic (ATP, pHi) status...
October 3, 2016: Metabolites
https://www.readbyqxmd.com/read/27689878/deficiency-of-parkinson-s-disease-related-gene-fbxo7-is-associated-with-impaired-mitochondrial-metabolism-by-parp-activation
#19
Marta Delgado-Camprubi, Noemi Esteras, Marc Pm Soutar, Helene Plun-Favreau, Andrey Y Abramov
The Parkinson's disease (PD)-related protein F-box only protein 7 (Fbxo7) is the substrate-recognition component of the Skp1-Cullin-F-box protein E3 ubiquitin ligase complex. We have recently shown that PD-associated mutations in Fbxo7 disrupt mitochondrial autophagy (mitophagy), suggesting a role for Fbxo7 in modulating mitochondrial homeostasis. Here we report that Fbxo7 deficiency is associated with reduced cellular NAD(+) levels, which results in increased mitochondrial NADH redox index and impaired activity of complex I in the electron transport chain...
September 30, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27634671/pharmacological-inhibition-of-nox4-ameliorates-alcohol-induced-liver-injury-in-mice-through-improving-oxidative-stress-and-mitochondrial-function
#20
Qian Sun, Wenliang Zhang, Wei Zhong, Xinguo Sun, Zhanxiang Zhou
BACKGROUND: Oxidative stress plays a crucial role in the development of alcoholic liver disease (ALD), however effective pharmacological treatment for oxidative injury is still lacking. The objective of this study was to determine whether inhibition of NADPH oxidase activity could reverse alcohol-induced liver injury via protecting mitochondrial functions. METHODS: C57BL/6J mice were pair-fed with Lieber-DeCarli control or ethanol diet for four week with or without administration with 30mg/kg/d GKT137831, a NOX4 inhibitor for the last two weeks...
September 12, 2016: Biochimica et Biophysica Acta
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