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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
Dan Y Gui, Lucas B Sullivan, Alba Luengo, Aaron M Hosios, Lauren N Bush, Nadege Gitego, Shawn M Davidson, Elizaveta Freinkman, Craig J Thomas, Matthew G Vander Heiden
Metformin use is associated with reduced cancer mortality, but how metformin impacts cancer outcomes is controversial. Although metformin can act on cells autonomously to inhibit tumor growth, the doses of metformin that inhibit proliferation in tissue culture are much higher than what has been described in vivo. Here, we show that the environment drastically alters sensitivity to metformin and other complex I inhibitors. We find that complex I supports proliferation by regenerating nicotinamide adenine dinucleotide (NAD)+, and metformin's anti-proliferative effect is due to loss of NAD+/NADH homeostasis and inhibition of aspartate biosynthesis...
October 12, 2016: Cell Metabolism
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
Reiko Sanokawa-Akakura, Shin Akakura, Siamak Tabibzadeh
Recent evidence suggests that hydrogen sulfide (H2S) has cytoprotective and anti-aging effects. However, the mechanisms for such properties are not fully understood. Here, we show that the expression of the main H2S producing enzyme, CBS, and production of H2S are coordinately diminished in replicative senescent adult human dermal fibroblasts. The reduced production of H2S falls within the same time-frame that the hallmarks of replicative senescence appear including accumulation of SA-β-Gal, enhanced expression of p16, p21, and RRM2B while the expression of RRM2, hTERT, SIRT1, NAMPT, and NAD/NADH ratio all fall...
2016: PloS One
Hongyun Nie, Maiqian Nie, Ting Xiao, Yan Wang, Xiaoting Tian
For further understanding of the roles of small organic acids commonly produced during alkane degradation, glutaric acid was found to be effective for promoting hexadecane degradation by P. aeruginosa NY3. Our results demonstrated that the synchronous metabolism of glutaric acid could increase both the growth rates and hexadecane degradation ability of P. aeruginosa NY3. Glutaric acid was proved to be able to increase the ratios of the concentrations of NAD(+) and NADH inside strain NY3 cells, and subsequently accelerated cell growth rates through improving electron respiration rates...
October 4, 2016: Science of the Total Environment
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
Liang Tian, Jonathan Lo, Xiongjun Shao, Tianyong Zheng, Daniel G Olson, Lee R Lynd
: Ferredoxin:NAD(+) oxidoreductase (NADH-FNOR) catalyzes the transfer of electrons from reduced ferredoxin to NAD(+) This enzyme has been hypothesized to be the main enzyme responsible for ferredoxin oxidization in the NADH-based ethanol pathway in Thermoanaerobacterium saccharolyticum, however, the corresponding gene has not yet been identified. Here, we identified the Tsac_1705 protein as a candidate FNOR based on the homology of its functional domains. We then confirmed its activity in vitro with a ferredoxin-based FNOR assay...
September 30, 2016: Applied and Environmental Microbiology
Rachel Cinco, Michelle A Digman, Enrico Gratton, Ulrike Luderer
Previous work characterizing ovarian bioenergetics has defined follicular metabolism by measuring metabolic byproducts in culture media. However, culture conditions perturb the native state of the follicle, and these methods do not distinguish between metabolism occurring within oocytes or granulosa cells. We applied the phasor approach to fluorescent lifetime imaging microscopy (Phasor FLIM) at 740 nm 2-photon excitation to examine the spatial distribution of free and protein-bound nicotinamide adenine dinucleotide hydride (NADH) during primordial through preovulatory stages of follicular development in fresh ex vivo murine neonatal and gonadotropin stimulated pre-pubertal ovaries...
September 28, 2016: Biology of Reproduction
Sang-Young Kim, Bruce M Cohen, Xi Chen, Scott E Lukas, Ann K Shinn, A Cagri Yuksel, Tao Li, Fei Du, Dost Öngür
Balance between the redox pair of nicotinamide adenine dinucleotides (oxidized NAD+ and reduced NADH), reflects the oxidative state of cells and the ability of biological systems to carry out energy production. A growing body of evidence suggests that an "immuno-oxidative" pathway including oxidative stress, mitochondrial dysfunction, neuroinflammation, and cell-mediated immune response may contribute to disruptions in brain activity in schizophrenia (SZ). The aim of this study is to assess possible redox imbalance in SZ patients by using a novel in vivo (31)P MRS technique...
September 24, 2016: Schizophrenia Bulletin
Guilherme Akio Tamura Ozaki, Regina Celi Trindade Camargo, Tatiana Emy Koike, Thiago Alves Garcia, Robson Chacon Castoldi, João Domingos Augusto Dos Santos Pereira, Carlos José Leopoldo Constantino, José Carlos Silva Camargo Filho
Treatment of muscle injuries usually results in the interruption of sports practice; thus, studies aimed at accelerating the return to activity, with proper tissue repair, are important. Therefore, this study aimed to evaluate the effects of photobiomodulation (PBM), associated or not with platelet-rich plasma (PRP), on the treatment of muscle injury. Thirty-five animals were used and divided into five groups (n = 7): control (C), control lesion (CL), lesion treated with low-level laser therapy (LLLT) (LLt), lesion treated with PRP (LP), and lesion treated with both techniques, LLLT and PRP (LLtP)...
September 20, 2016: Lasers in Medical Science
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
Min Li, Suzette Riddle, Hui Zhang, Angelo D'Alessandro, Amanda Flockton, Natalie J Serkova, Kirk C Hansen, Radu Moldvan, B Alexandre McKeon, Maria Frid, Sushil Kumar, Hong Li, Hongbing Liu, Angela Caánovas, Juan F Medrano, Milton G Thomas, Dijana Iloska, Lydie Plecitá-Hlavatá, Petr Ježek, Soni Pullamsetti, Mehdi A Fini, Karim C El Kasmi, QingHong Zhang, Kurt R Stenmark
BACKGROUND: Changes in metabolism have been suggested to contribute to the aberrant phenotype of vascular wall cells, including fibroblasts, in pulmonary hypertension (PH). Here, we test the hypothesis that metabolic reprogramming to aerobic glycolysis is a critical adaptation of fibroblasts in the hypertensive vessel wall that drives proliferative and proinflammatory activation through a mechanism involving increased activity of the NADH-sensitive transcriptional corepressor C-terminal binding protein 1 (CtBP1)...
October 11, 2016: Circulation
Andrew Jm Lewis, Jack Jj Miller, Chloe McCallum, Oliver J Rider, Stefan Neubauer, Lisa C Heather, Damian J Tyler
Metformin improves cardiovascular outcomes in type 2 diabetes, but its exact mechanisms of action remain controversial. We used hyperpolarized [1-(13)C]pyruvate magnetic resonance spectroscopy to determine the effects of metformin treatment upon heart and liver pyruvate metabolism in rats in vivo Both oral treatment for four weeks and a single intravenous metformin infusion significantly increased the cardiac [1-(13)C]lactate:[1-(13)C]pyruvate ratio, but had no effect on the [1-(13)C]bicarbonate + (13)CO2:[1-(13)C]pyruvate ratio, an index of pyruvate dehydrogenase flux...
August 25, 2016: Diabetes
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
Tiande Zou, Bing Yu, Jie Yu, Xiangbing Mao, Ping Zheng, Jun He, Zhiqing Huang, Yue Liu, Daiwen Chen
BACKGROUND: Mitochondria are of major importance in oocyte and early embryo, playing a key role in maintaining energy homeostasis. Epidemiological findings indicate that maternal undernutrition-induced mitochondrial dysfunction during pregnancy is associated with the development of metabolic disorders in offspring. Here, we investigated the effects of moderately decreased maternal energy intake during pregnancy on skeletal muscle mitochondrial biogenesis in fetal offspring with pig as a model...
2016: Genes & Nutrition
Chi Fung Lee, Juan D Chavez, Lorena Garcia-Menendez, Yongseon Choi, Nathan D Roe, Ying Ann Chiao, John S Edgar, Young Ah Goo, David R Goodlett, James E Bruce, Rong Tian
BACKGROUND: Impairments of mitochondrial function in the heart are linked intricately to the development of heart failure, but there is no therapy for mitochondrial dysfunction. METHODS: We assessed the reduced/oxidized ratio of nicotinamide adenine dinucleotide (NADH/NAD(+) ratio) and protein acetylation in the failing heart. Proteome and acetylome analyses were followed by docking calculation, mutagenesis, and mitochondrial calcium uptake assays to determine the functional role of specific acetylation sites...
September 20, 2016: Circulation
Fumihiko Hara, Junko Tatebe, Ippei Watanabe, Junichi Yamazaki, Takanori Ikeda, Toshisuke Morita
BACKGROUND: Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2on endothelial senescence and clarified the mechanisms involved. METHODS AND RESULTS: Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium...
August 25, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
Juliana Aparecida Ronchi, Annelise Francisco, Luiz Augusto Correa Passos, Tiago Rezende Figueira, Roger Frigério Castilho
The forward reaction of nicotinamide nucleotide transhydrogenase (NNT) reduces NADP(+) at the expense of NADH oxidation and H(+) movement down the electrochemical potential across the inner mitochondrial membrane, establishing an NADPH/NADP(+) ratio severalfold higher than the NADH/NAD(+) ratio in the matrix. In turn, NADPH drives processes, such as peroxide detoxification and reductive biosynthesis. In this study, we generated a congenic mouse model carrying a mutated Nnt(C57BL/6J) allele from the C57BL/6J substrain...
September 16, 2016: Journal of Biological Chemistry
Sarika Srivastava
Nicotinamide adenine dinucleotide (NAD(+)) is a central metabolic cofactor in eukaryotic cells that plays a critical role in regulating cellular metabolism and energy homeostasis. NAD(+) in its reduced form (i.e. NADH) serves as the primary electron donor in mitochondrial respiratory chain, which involves adenosine triphosphate production by oxidative phosphorylation. The NAD(+)/NADH ratio also regulates the activity of various metabolic pathway enzymes such as those involved in glycolysis, Kreb's cycle, and fatty acid oxidation...
December 2016: Clinical and Translational Medicine
Paula Simó-Mirabet, Azucena Bermejo-Nogales, Josep Alvar Calduch-Giner, Jaume Pérez-Sánchez
The seven sirtuin (SIRT) counterparts of higher vertebrates were identified and molecularly characterized in a farmed fish of the Sparidae family, order Perciformes. These proteins are NAD(+)-dependent deacetylases that couple protein deacetylation with the energy status of the cell via the cellular NAD(+)/NADH ratio with a strict conservation of the characteristic catalytic domain surrounded by divergent N- and C- terminal regions. Phylogenetic analysis showed three major clades corresponding to SIRT1-3, SIRT4-5, and SIRT6-7 that reflected the present hierarchy of vertebrates and the accepted classification of SIRTs...
July 18, 2016: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
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