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Igor Florez-Sarasa, Ko Noguchi, Wagner Araujo, 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 on dissipating the excess of reductant power from the chloroplast...
October 19, 2016: Plant Physiology
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 are 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...
October 14, 2016: Journal of Neurochemistry
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
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
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
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
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
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
Natalia Niedźwiecka, Jadwiga Gronczewska, Edward F Skorkowski
Herring spermatozoa exhibit a high activity of NAD-preferring malic enzyme (NAD-ME). This enzyme is involved in the generation of NADH or NADPH in the decarboxylation of malate to form pyruvate and requires some divalent cations to express its activity. In order to confirm that NAD-ME isolated from herring sperm cells is localized in mitochondria, we performed immunofluorescent analysis and assayed spectrophotometrically the malic enzyme reaction. Production of polyclonal rabbit antibodies against NAD-ME from herring spermatozoa enabled identification of mitochondrial localization of this enzyme inside herring spermatozoa...
September 14, 2016: Fish Physiology and Biochemistry
David A Stroud, Elliot E Surgenor, Luke E Formosa, Boris Reljic, Ann E Frazier, Marris G Dibley, Laura D Osellame, Tegan Stait, Traude H Beilharz, David R Thorburn, Agus Salim, Michael T Ryan
Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans, making it one of the largest known multi-subunit membrane protein complexes. Complex I exists in supercomplex forms with respiratory chain complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP. Complex I is also a major source of damaging reactive oxygen species and its dysfunction is associated with mitochondrial disease, Parkinson's disease and ageing...
September 14, 2016: Nature
Hyun Seung Ban, Xuezhen Xu, Kusik Jang, Inhyub Kim, Bo-Kyung Kim, Kyeong Lee, Misun Won
We previously reported that hypoxia-inducible factor (HIF)-1 inhibitor LW6, an aryloxyacetylamino benzoic acid derivative, inhibits malate dehydrogenase 2 (MDH2) activity during the mitochondrial tricarboxylic acid (TCA) cycle. In this study, we present a novel MDH2 inhibitor compound 7 containing benzohydrazide moiety, which was identified through structure-based virtual screening of chemical library. Similar to LW6, compound 7 inhibited MDH2 activity in a competitive fashion, thereby reducing NADH level. Consequently, compound 7 reduced oxygen consumption and ATP production during the mitochondrial respiration cycle, resulting in increased intracellular oxygen concentration...
2016: PloS One
Nima N Naseri, Joseph Bonica, Hui Xu, Larry C Park, Jamshid Arjomand, Zhengming Chen, Gary E Gibson
Metabolic dysfunction is well-documented in Huntington's disease (HD). However, the link between the mutant huntingtin (mHTT) gene and the pathology is unknown. The tricarboxylic acid (TCA) cycle is the main metabolic pathway for the production of NADH for conversion to ATP via the electron transport chain (ETC). The objective of this study was to test for differences in enzyme activities, mRNAs and protein levels related to the TCA cycle between lymphoblasts from healthy subjects and from patients with HD...
2016: PloS One
Ziwei Dai, Alexander A Shestov, Luhua Lai, Jason W Locasale
The Warburg effect, or aerobic glycolysis, is marked by the increased metabolism of glucose to lactate in the presence of oxygen. Despite its widespread prevalence in physiology and cancer biology, the causes and consequences remain incompletely understood. Here, we show that a simple balance of interacting fluxes in glycolysis creates constraints that impose the necessary conditions for glycolytic flux to generate lactate as opposed to entering into the mitochondria. These conditions are determined by cellular redox and energy demands...
September 6, 2016: Biophysical Journal
Gabriele Giachin, Romain Bouverot, Samira Acajjaoui, Serena Pantalone, Montserrat Soler-López
Neurons are extremely energy demanding cells and highly dependent on the mitochondrial oxidative phosphorylation (OXPHOS) system. Mitochondria generate the energetic potential via the respiratory complexes I to IV, which constitute the electron transport chain (ETC), together with complex V. These redox reactions release energy in the form of ATP and also generate reactive oxygen species (ROS) that are involved in cell signaling but can eventually lead to oxidative stress. Complex I (CI or NADH:ubiquinone oxidoreductase) is the largest ETC enzyme, containing 44 subunits and the main contributor to ROS production...
2016: Frontiers in Molecular Biosciences
A Kamali Sangani, A A Masoudi, R Vaez Torshizi
The objectives of the current study were to investigate the activity of the electron transport chain (ETC) complexes, adenosine triphosphate (ATP), and reactive oxygen species (ROS) in the sperm mitochondria of 2 Iranian slow- and fast-growing chickens, namely native and Aryan strains. In this study, semen of 133 roosters was analyzed by computer-assisted sperm analysis (CASA). The roosters were categorized by sperm progressivity, as a low or high sperm motility phenotype. Mitochondrial complex I (NADH ubiquinone oxidoreductase), II (succinate dehydrogenase), III (ubiquinol cytochrome C reductase), IV (cytochrome C oxidase) activity, ATP, and ROS production in sperm were assayed...
September 2, 2016: Poultry Science
Gisela Beutner, Alavian N Kambiz, Elizabeth A Jonas, George A Porter
Mitochondrial ATP generation by oxidative phosphorylation combines the stepwise oxidation by the electron transport chain (ETC) of the reducing equivalents NADH and FADH2 with the generation of ATP by the ATP synthase. Recent studies show that the ATP synthase is not only essential for the generation of ATP but may also contribute to the formation of the mitochondrial permeability transition pore (PTP). We present a model, in which the PTP is located within the c-subunit ring in the Fo subunit of the ATP synthase...
September 3, 2016: Handbook of Experimental Pharmacology
Mahsa Ranji, Mohammad Masoudi Motlagh, Fahimeh Salehpour, Reyhaneh Sepehr, James S Heisner, Ranjan K Dash, Amadou K S Camara
Oxidation of substrates to generate ATP in mitochondria is mediated by redox reactions of NADH and FADH2. Cardiac ischemia and reperfusion (IR) injury compromises mitochondrial oxidative phosphorylation. We hypothesize that IR alters the metabolic heterogeneity of mitochondrial redox state of the heart that is only evident in the 3-D optical cryoimaging of the perfused heart before, during, and after IR. The study involved four groups of hearts: time control (TC: heart perfusion without IR), global ischemia (Isch), global ischemia followed by reperfusion (IR) and TC with PCP (a mitochondrial uncoupler) perfusion...
2016: IEEE Journal of Translational Engineering in Health and Medicine
Chris Habrian, Adithi Chandrasekhara, Bita Shahrvini, Brian Hua, Jason Lee, Roger Jesinghaus, Rachael Barry, Zemer Gitai, Justin Kollman, Enoch P Baldwin
CTP synthetases catalyze the last step of pyrimidine biosynthesis and provide the sole de novo source of cytosine-containing nucleotides. As a central regulatory hub, they are regulated by ribonucleotide and enzyme concentration through ATP and UTP substrate availability, CTP product inhibition, GTP allosteric modification, and quaternary structural changes including the formation of CTP-inhibited linear polymers (filaments). Here, we demonstrate that nicotinamide redox cofactors are moderate inhibitors of Escherichia coli CTP synthetase (EcCTPS)...
October 4, 2016: Biochemistry
Gangarao Davuluri, Allawy Allawy, Samjhana Thapaliya, Julie H Rennison, Dharmvir Singh, Avinash Kumar, Yana Sandlers, David R Van Wagoner, Chris A Flask, Charles Hoppel, Takhar Kasumov, Srinivasan Dasarathy
Ammonia is a cytotoxic metabolite that is removed primarily by hepatic ureagenesis in humans. Hyperammonemia occurs in advanced hepatic, cardiac, pulmonary disease, and in urea cycle enzyme deficiencies. Increased skeletal muscle ammonia uptake and metabolism are the major mechanism of non-hepatic ammonia disposal. Non-hepatic ammonia disposal occurs in the mitochondria via glutamate synthesis from α-ketoglutarate resulting in cataplerosis. We show skeletal muscle mitochondrial dysfunction during hyperammonemia in a comprehensive array of human, rodent and cellular models...
August 25, 2016: Journal of Physiology
Ruilian Yao, Dewang Xiong, Hongbo Hu, Masataka Wakayama, Wenjuan Yu, Xuehong Zhang, Kazuyuki Shimizu
BACKGROUND: Glycerol, a byproduct of biodiesel, has become a readily available and inexpensive carbon source for the production of high-value products. However, the main drawback of glycerol utilization is the low consumption rate and shortage of NADPH formation, which may limit the production of NADPH-requiring products. To overcome these problems, we constructed a carbon catabolite repression-negative ΔptsGglpK* mutant by both blocking a key glucose PTS transporter and enhancing the glycerol conversion...
2016: Biotechnology for Biofuels
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