Página 1 dos resultados de 2413 itens digitais encontrados em 0.081 segundos

Mentha aquatica L. extract affects mitochondrial bioenergetics

Ferreira, Fernanda M.; Pereira, Olívia R.; Cardoso, Susana M.; Oliveira, Paulo J.; Moreno, António J.M.
Fonte: European Society for Clinical Investigation Publicador: European Society for Clinical Investigation
Tipo: Conferência ou Objeto de Conferência
Português
Relevância na Pesquisa
36.82%
Mentha aquatica extracts are commonly used in food flavoring and pharmacology. In the present work, we evaluated the possible effects of Mentha aquatica L. (water mint) ethanolic extract on rat liver mitochondria bioenergetics. Rat liver mitochondria were isolated using conventional protocols. M. aquatica extracts were evaluated on mitochondrial membrane electric potential by using a tetraphenylphosphonium cation (TPP+)-selective electrode, while mitochondrial respiratory activity was evaluated using a Clark-type oxygen electrode, either in the presence of glutamate + malate and succinate as respiratory substrates. Mitochondrial osmotic volume changes were measured by the pseudo-absorbance changes at 520 nm with a suitable spectrophotometer- recorder set up. Incubation of M. aquatica extracts with isolated liver mitochondria resulted in a decrease in mitochondrial oxidative phsophorylation, reflected both by a decrease in respiratory parameters (state 3, respiratory control ratio -RCR, uncoupled respiration) and in membrane electric potential. This decrease can probably be related with the polyphenolic composition of the extract (mainly eriodictyol-7-O-rutinoside, luteolin-7-O-rutinoside, naringenin-7-O-rutinoside, hesperitin-7-O-rutinoside and rosmarinic acid)...

Mentha aquatica L. extract affects mitochondrial bioenergetics

Ferreira, Fernanda M.; Pereira, Olívia R.; Cardoso, Susana M.; Oliveira, Paulo J.; Moreno, António J.M.
Fonte: European Journal of Clinical Investigation Publicador: European Journal of Clinical Investigation
Tipo: Conferência ou Objeto de Conferência
Português
Relevância na Pesquisa
36.82%
Mentha aquatica extracts are commonly used in food flavoring and pharmacology. In the present work, we evaluated the possible effects of Mentha aquatica L. (water mint) ethanolic extract on rat liver mitochondria bioenergetics. Rat liver mitochondria were isolated using conventional protocols. M. aquatica extracts were evaluated on mitochondrial membrane electric potential by using a tetraphenylphosphonium cation (TPP+)-selective electrode, while mitochondrial respiratory activity was evaluated using a Clark-type oxygen electrode, either in the presence of glutamate + malate and succinate as respiratory substrates. Mitochondrial osmotic volume changes were measured by the pseudo-absorbance changes at 520 nm with a suitable spectrophotometer- recorder set up. Incubation of M. aquatica extracts with isolated liver mitochondria resulted in a decrease in mitochondrial oxidative phsophorylation, reflected both by a decrease in respiratory parameters (state 3, respiratory control ratio -RCR, uncoupled respiration) and in membrane electric potential. This decrease can probably be related with the polyphenolic composition of the extract (mainly eriodictyol-7-O-rutinoside, luteolin-7-O-rutinoside, naringenin-7-O-rutinoside, hesperitin-7-O-rutinoside and rosmarinic acid)...

Mentha aquatica L. extract effects on mitochondrial bioenergetics

Ferreira, Fernanda M.; Pereira, Olívia R.; Cardoso, Susana M.; Oliveira, Paulo J.; Moreno, António J. M.
Fonte: Elsevier Publicador: Elsevier
Tipo: Conferência ou Objeto de Conferência
Português
Relevância na Pesquisa
36.96%
Mentha aquatica (water mint) extracts are regularly used in food flavoring and pharmacology. In the present study, the possible effects of an ethanolic extract from leaves of M. aquatica L. on rat liver mitochondria bioenergetics were evaluated. The plant extract (25 μg•mg protein− 1) but not the vehicle, inhibited the mitochondrial oxidative system, as seen by a depression of respiration (state 3, respiratory control ratio (RCR), FCCP-stimulated respiration) and lower generation of the transmembrane electric potential using glutamate + malate and succinate as respiratory substrates. The depressing effects in oxidative phosphorylation can probably be related with the polyphenolic composition of the extract (mainly eriodictyol-7-O-rutinoside, luteolin-7-O-rutinoside, naringenin-7-O-rutinoside, hesperitin-7-O-rutinoside and rosmarinic acid) that can interact with membrane and change the inner mitochondrial membrane lipidic moiety. Despite decreasing the RCR, the presence of M. aquatica extract did not affect the mitochondrial phosphorylative capacity, as estimated by the ADP/O ratio. No significant increase in inner mitochondrial membrane permeability was observed and induction of mitochondrial permeability transition pore was not altered in the range of concentrations tested (up to 25 μg•mg protein− 1) either. For the highest concentrations tested (25 μg•mg protein− 1 or higher) the inhibition observed on the mitochondrial respiratory chain...

Mentha aquatica L. extract effects on mitochondrial bioenergetics

Ferreira, Fernanda M.; Pereira, Olívia R.; Cardoso, Susana M.; Oliveira, Paulo J.; Moreno, António J.M.
Fonte: Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biologia Publicador: Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biologia
Tipo: Conferência ou Objeto de Conferência
Português
Relevância na Pesquisa
36.96%
Mentha aquatica (water mint) extracts are regularly used in food flavoring and pharmacology. In the present study, the possible effects of an ethanolic extract from leaves of M. aquatica L. on rat liver mitochondria bioenergetics were evaluated. The plant extract (25 μg·mg protein−1) but not the vehicle, inhibited the mitochondrial oxidative system, as seen by a depression of respiration (state 3, respiratory control ratio (RCR), FCCP stimulated respiration) and lower generation of the transmembrane electric potential using glutamate+malate and succinate as respiratory substrates. The depressing effects in oxidative phosphorylation can probably be related with the polyphenolic composition of the extract (mainly eriodictyol-7-O-rutinoside, luteolin-7-O-rutinoside, naringenin- 7-O-rutinoside, hesperitin-7-O-rutinoside and rosmarinic acid) that can interact with membrane and change the inner mitochondrial membrane lipidic moiety. Despite decreasing the RCR, the presence of M. aquatica extract did not affect the mitochondrial phosphorylative capacity, as estimated by the ADP/O ratio. No significant increase in inner mitochondrial membrane permeability was observed and induction of mitochondrial permeability transition pore was not altered in the range of concentrations tested (up to 25 μg·mg protein−1) either. For the highest concentrations tested (25 μg·mg protein−1 or higher) the inhibition observed on the mitochondrial respiratory chain...

Comparative effects of three 1,4-dihydropyridine derivatives [OSI-1210, OSI-1211 (etaftoron), and OSI-3802] on rat liver mitochondrial bioenergetics and on the physical properties of membrane lipid bilayers: Relevance to the length of the alkoxyl chain in positions 3 and 5 of the DHP ring

Fernandes, Maria A. S.; Pereira, Susana P. S.; Jurado, Amália S.; Custódio, José B. A.; Santos, Maria S.; Moreno, António J. M.; Duburs, Gunars; Vicente, Joaquim A. F.
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
Português
Relevância na Pesquisa
36.96%
The 1,4-dihydropyridines OSI-1210, OSI-1211 (etaftoron), and OSI-3802 are compounds with similar chemical structure. They differ by the length of the alkoxyl chain in positions 3 and 5 of the dihydropyridine (DHP) ring and by their pharmacological action characteristics. However, as far as we know, a clear relationship between the effects of these compounds and the length of the alkoxyl chain in positions 3 and 5 of the DHP has not been established. The goal of this study was to compare the influence of OSI-1210, OSI-1211 (etaftoron), and OSI-3802 on rat liver mitochondrial bioenergetics and on the physical properties of membrane lipid bilayers, correlating their actions with the length of the alkoxyl chain in positions 3 and 5 of the DHP ring. Using either glutamate/malate or succinate as respiratory substrates, all the compounds, in concentrations of up to 500 [mu]M, depressed state 3 and uncoupled respiration, respiratory control (RCR) and ADP/O ratios, and phosphorylation rate, whereas state 4 respiration was stimulated. However, the stimulatory effect on state 4 induced by OSI-3802, the compound with the longest chain in positions 3 and 5 of the DHP ring, as well as its inhibitory effects on RCR and ADP/O ratios and phosphorylation rate were more pronounced than that induced by OSI-1210 and OSI-1211 (etaftoron)...

Evaluation of olive oil mill wastewater toxicity on the mitochondrial bioenergetics after treatment with Candida oleophila

Peixoto, F.; Martins, F.; Amaral, C.; Gomes-Laranjo, J.; Almeida, J.; Palmeira, C. M.
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
Português
Relevância na Pesquisa
36.82%
In a previous work the ability of Candida oleophila to use phenolic compounds as sole carbon and energy source at high concentrations without an additional carbon source was reported. C. oleophila grown in bioreactor batch cultures in a diluted and sterilized olive oil mill wastewater (OMW) caused a significant decrease in the total tannins content but no significant alteration was observed in phenolic acid and fatty acid content. Both treated and untreated OMWs were tested to evaluate the capacity in interfering with mitochondrial bioenergetics. Mitochondrial respiration was not affected by treated OMW on the range of used concentrations, contrary to the untreated OMW. Furthermore, mitochondrial membrane potential and respiratory complexes were always significantly less affected by treated OMW in comparison with untreated OMW. However, supplementary treatment should be applied before OMW could be considered non-toxic.; http://www.sciencedirect.com/science/article/B6WDM-4RTCPRB-1/1/334fdd68f295b113386cc5d47b47d620

Effects of 1,4-dihydropyridine derivatives (cerebrocrast, gammapyrone, glutapyrone, and diethone) on mitochondrial bioenergetics and oxidative stress: a comparative study

Fernandes, Maria A. S.; Santos, Maria S.; Vicente, Joaquim A. F.; Moreno, António J. M.; Velena, Astrida; Duburs, Gunars; Oliveira, Catarina R.
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
Português
Relevância na Pesquisa
37.12%
The potential protective action of 1,4-dihydropyridine derivatives (cerebrocrast, gammapyrone, glutapyrone, and diethone) against oxidative stress was assessed on mitochondrial bioenergetics, inner membrane anion channel (IMAC), Ca2+-induced opening of the permeability transition pore (PTP), and oxidative damage induced by the oxidant pair adenosine diphosphate (ADP)/Fe2+ (lipid peroxidation) of mitochondria isolated from rat liver. By using succinate as the respiratory substrate, respiratory control ratio (RCR), ADP to oxygen ratio (ADP/O), state 3, state 4, and uncoupled respiration rates were not significantly affected by gammapyrone, glutapyrone, and diethone concentrations up to 100 [mu]M. Cerebrocrast at concentrations higher than 25 [mu]M depressed RCR, ADP/O, state 3, and uncoupled respiration rates, but increased three times state 4 respiration rate. The transmembrane potential ([Delta][Psi]) and the phosphate carrier rate were also decreased. At concentrations lower than 25 [mu]M, cerebrocrast inhibited the mitochondrial IMAC and partially prevented Ca2+-induced opening of the mitochondrial PTP, whereas gammapyrone, glutapyrone, and diethone were without effect. Cerebrocrast, gammapyrone, and glutapyrone concentrations up to 100 [mu]M did not affect ADP/Fe2+-induced lipid peroxidation of rat liver mitochondria...

Rapeseed oil‑rich diet alters hepatic mitochondrial membrane lipid composition and disrupts bioenergetics

Monteiro, João P.; Pereira, Cláudia V.; Silva, Ana M.; Maciel, Elisabete; Baldeiras, Inês; Peixoto, Francisco; Domingues, Maria R.; Jurado, Amália S.; Oliveira, Paulo J.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.96%
Diet is directly related with physiological alterations occurring at a cell and subcellular level. However, the role of diet manipulation on mitochondrial physiology is still largely unexplored. Aiming at correlating diet with alterations of mitochondrial membrane composition and bioenergetics, Wistar-Han male rats were fed for 11, 22 and 33 days with a rapeseed oil-based diet and mitochondrial bioenergetics, and membrane composition were compared at each time point with a standard diet group. Considerable differences were noticed in mitochondrial membrane lipid composition, namely in terms of fatty acyl chains and relative proportions of phospholipid classes, the modified diet inducing a decrease in the saturated to unsaturated molar ratio and an increase in the phosphatidylcholine to phosphatidylethanolamine molar ratio. Mass spectrometry lipid analysis showed significant differences in the major species of cardiolipin, with an apparent increased incorporation of oleic acid as a result of exposure to the modified diet. Rats fed the modified diet during 22 days showed decreased hepatic mitochondrial state 3 respiration and were more susceptible to Ca2+-induced transition pore opening. Rapeseed oil-enriched diet also appeared to promote a decrease in hydroperoxide production by the respiratory chain...

Pre-diabetes alters testicular PGC1-α/SIRT3 axis modulating mitochondrial bioenergetics and oxidative stress

Rato, Luis; Duarte, Ana I.; Tomás, Gonçalo D.; Santos, M. S.; Moreira, Paula I.; Socorro, Silvia; Cavaco, José E.; Alves, Marco G.; Oliveira, Pedro F.
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.82%
Pre-diabetes, a risk factor for type 2 diabetes development, leads to metabolic changes at testicular level. Peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α) and Sirtuin 3 (Sirt3) are pivotal inmitochondrial function. We hypothesized that pre-diabetes disrupts testicular PGC-1α/Sirt3 axis, compromising testicular mitochondrial function. Using a high-energy-diet induced pre-diabetic rat model, we evaluated testicular levels of PGC-1α and its downstream targets, nuclear respiratory factors 1 (NRF-1) and 2 (NRF-2),mitochondrial transcription factor A (TFAM) and Sirt3.We also assessedmitochondrial DNA (mtDNA) content, mitochondrial function, energy levels and oxidative stress parameters. Protein levels were quantified by Western Blot, mtDNA contentwas determined by qPCR.Mitochondrial complex activity and oxidative stress parameterswere spectrophotometrically evaluated. Adenine nucleotide levels, adenosine and its metabolites (inosine and hypoxanthine) were determined by reverse-phase HPLC. Pre-diabetic rats showed increased blood glucose levels and impaired glucose tolerance. Both testicular PGC-1α and Sirt3 levels were decreased. NRF-1, NRF-2 and TFAM were not altered. Testicular mtDNA content was decreased. Mitochondrial complex I activity was increased...

Comparative effects of lantadene A and its reduced metabolite on mitochondrial bioenergetics

GARCIA, Andrea F.; MEDEIROS, Hyllana C. D.; MAIOLI, Marcos A.; LIMA, Michele C.; ROCHA, Bruno A.; COSTA, Fernando B. da; CURTI, Carlos; GROPPO, Milton; MINGATTO, Fabio E.
Fonte: PERGAMON-ELSEVIER SCIENCE LTD Publicador: PERGAMON-ELSEVIER SCIENCE LTD
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.96%
Lantana (Lantana camara Linn.) is a noxious weed to which certain medicinal properties have been attributed, but its ingestion has been reported to be highly toxic to animals and humans, especially in the liver. The main hepatotoxin in lantana leaves is believed to be the pentacyclic triterpenoid lantadene A (LA), but the precise mechanism by which it induces hepatotoxicity has not yet been established. This work addressed the action of LA and its reduced derivative (RLA) on mitochondrial bioenergetics. At the concentration range tested (5-25 mu M), RLA stimulated state-4 respiration, inhibited state-3 respiration, circumvented oligomycin-inhibited state-3 respiration, dissipated membrane potential and depleted ATP in a concentration-dependent manner. However. LA did not stimulate state-4 respiration, nor did it affect the other mitochondrial parameters to the extent of its reduced derivative. The lantadenes didn`t inhibit the CCCP-uncoupled respiration but increased the ATPase activity of intact coupled mitochondria. The ATPase activity of intact uncoupled or disrupted mitochondria was not affected by the compounds. We propose, therefore, that RLA acts as a mitochondrial uncoupler of oxidative phosphorylation, a property that arises from the biotransformation (reduction) of LA...

Cellular bioenergetics after erythropoietin therapy in chronic renal failure.

Marrades, R M; Alonso, J; Roca, J; González de Suso, J M; Campistol, J M; Barberá, J A; Diaz, O; Torregrosa, J V; Masclans, J R; Rodríguez-Roisin, R; Wagner, P D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/05/1996 Português
Relevância na Pesquisa
27.05%
After erythropoietin (rHuEPO) therapy, patients with chronic renal failure (CRF) do not improve peak O2 uptake (VO2 peak) as much as expected from the rise in hemoglobin concentration ([Hb]). In a companion study, we explain this phenomenon by the concurrent effects of fall in muscle blood flow after rHuEPO and abnormal capillary O2 conductance observed in CRF patients. The latter is likely associated with a poor muscle microcirculatory network and capillary-myofiber dissociation due to uremic myopathy. Herein, cellular bioenergetics and its relationships with muscle O2 transport, before and after rHuEPO therapy, were examined in eight CRF patients (27 +/- 7.3 [SD] yr) studied pre- and post-rHuEPO ([Hb] = 7.8 +/- 0.7 vs. 11.7 +/- 0.7 g x dl-1) during an incremental cycling exercise protocol. Eight healthy sedentary subjects (26 +/- 3.1 yr) served as controls. We hypothesize that uremic myopathy provokes a cytosolic dysfunction but mitochondrial oxidative capacity is not abnormal. 31P-nuclear magnetic resonance spectra (31P-MRS) from the vastus medialis were obtained throughout the exercise protocol consisting of periods of 2 min exercise (at 1.67 Hz) at increasing work-loads interspersed by resting periods of 2.5 min. On a different day...

PGC-1α Integrates Insulin Signaling, Mitochondrial Regulation, and Bioenergetic Function in Skeletal Muscle*S⃞

Pagel-Langenickel, Ines; Bao, Jianjun; Joseph, Joshua J.; Schwartz, Daniel R.; Mantell, Benjamin S.; Xu, Xiuli; Raghavachari, Nalini; Sack, Michael N.
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
Publicado em 15/08/2008 Português
Relevância na Pesquisa
27.17%
The pathophysiology underlying mitochondrial dysfunction in insulin-resistant skeletal muscle is incompletely characterized. To further delineate this we investigated the interaction between insulin signaling, mitochondrial regulation, and function in C2C12 myotubes and in skeletal muscle. In myotubes elevated insulin and glucose disrupt insulin signaling, mitochondrial biogenesis, and mitochondrial bioenergetics. The insulin-sensitizing thiazolidinedione pioglitazone restores these perturbations in parallel with induction of the mitochondrial biogenesis regulator PGC-1α. Overexpression of PGC-1α rescues insulin signaling and mitochondrial bioenergetics, and its silencing concordantly disrupts insulin signaling and mitochondrial bioenergetics. In primary skeletal myoblasts pioglitazone also up-regulates PGC-1α expression and restores the insulin-resistant mitochondrial bioenergetic profile. In parallel, pioglitazone up-regulates PGC-1α in db/db mouse skeletal muscle. Interestingly, the small interfering RNA knockdown of the insulin receptor in C2C12 myotubes down-regulates PGC-1α and attenuates mitochondrial bioenergetics. Concordantly, mitochondrial bioenergetics are blunted in insulin receptor knock-out mouse-derived skeletal myoblasts. Taken together these data demonstrate that elevated glucose and insulin impairs and pioglitazone restores skeletal myotube insulin signaling...

Measurement of Instantaneous Velocity Vectors of Organelle Transport: Mitochondrial Transport and Bioenergetics in Hippocampal Neurons

Gerencser, Akos A.; Nicholls, David G.
Fonte: The Biophysical Society Publicador: The Biophysical Society
Tipo: Artigo de Revista Científica
Publicado em 15/09/2008 Português
Relevância na Pesquisa
36.82%
Impaired transport of mitochondria, in dendrites and axons of neurons, and bioenergetic deficit are increasingly recognized to be of pathological importance in neurodegenerative diseases. To study the relationship between transport and bioenergetics, we have developed what to our knowledge is a novel technique to quantify organelle velocity in cultured cells. The aim was to combine measurement of motion and bioenergetic parameters while minimizing photodynamic oxidative artifacts evoked by fluorescence excitation. Velocity determination from sequential fluorescence images is not trivial, and here we describe an application of “optical flow”, the flow of gray values in grayscale images, to this problem. Based on the principles of photon shot noise occurring in low light level fluorescence microscopy, we describe and validate here an optical flow-based, robust method to measure velocity vectors for organelles expressing fluorescent proteins. This method features instantaneous velocity determination from a pair of images by detecting motion of edges, with no assumptions about the separation or shapes of the objects in the image. Optical flow was used in combination with single mitochondrion assay of mitochondrial thiol redox status by mitochondrially targeted redox-sensitive green fluorescent protein and measurement of mitochondrial membrane potential by tetramethylrhodamine methyl ester. Mitochondrial populations of resting cultured hippocampal neurons were analyzed. It was found that mitochondria with more oxidized thiol redox status have lower membrane potentials and are smaller in size. These mitochondria are more motile than the average; however...

Modeling Mitochondrial Bioenergetics with Integrated Volume Dynamics

Bazil, Jason N.; Buzzard, Gregery T.; Rundell, Ann E.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.12%
Mathematical models of mitochondrial bioenergetics provide powerful analytical tools to help interpret experimental data and facilitate experimental design for elucidating the supporting biochemical and physical processes. As a next step towards constructing a complete physiologically faithful mitochondrial bioenergetics model, a mathematical model was developed targeting the cardiac mitochondrial bioenergetic based upon previous efforts, and corroborated using both transient and steady state data. The model consists of several modified rate functions of mitochondrial bioenergetics, integrated calcium dynamics and a detailed description of the K+-cycle and its effect on mitochondrial bioenergetics and matrix volume regulation. Model simulations were used to fit 42 adjustable parameters to four independent experimental data sets consisting of 32 data curves. During the model development, a certain network topology had to be in place and some assumptions about uncertain or unobserved experimental factors and conditions were explicitly constrained in order to faithfully reproduce all the data sets. These realizations are discussed, and their necessity helps contribute to the collective understanding of the mitochondrial bioenergetics.

Essential Regulation of Cell Bioenergetics By Constitutive InsP3 Receptor Ca2+ Transfer to Mitochondria

Cárdenas, César; Miller, Russell A.; Smith, Ian; Bui, Thi; Molgó, Jordi; Müller, Marioly; Vais, Horia; Cheung, King-Ho; Yang, Jun; Parker, Ian; Thompson, Craig; Birnbaum, Morris; Hallows, Kenneth R.; Foskett, J. Kevin
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 23/07/2010 Português
Relevância na Pesquisa
26.96%
Mechanisms that regulate cellular metabolism are a fundamental requirement of all cells. Most eukaryotic cells rely on aerobic mitochondrial metabolism to generate ATP. Nevertheless, regulation of mitochondrial activity is incompletely understood. Here we identified an unexpected and essential role for constitutive InsP3R-mediated Ca2+ release in maintaining cellular bioenergetics. Macroautophagy provides eukaryotes with an adaptive response to nutrient deprivation that prolongs survival. Constitutive InsP3R Ca2+ signaling is required for macroautophagy suppression in cells in nutrient-replete media. In its absence, cells become metabolically compromised due to diminished mitochondrial Ca2+ uptake. Mitochondrial uptake of InsP3R released Ca2+ is fundamentally required to provide optimal bioenergetics by providing sufficient reducing equivalents to support oxidative phosphorylation. Absence of this Ca2+ transfer results in enhanced phosphorylation of pyruvate dehydrogenase and activation of AMPK, which activates pro-survival macroautophagy. Thus, constitutive InsP3R Ca2+ release to mitochondria is an essential cellular process that is required for efficient mitochondrial respiration and maintenance of normal cell bioenergetics.

Inhibition of Nicotinamide Phosphoribosyltransferase: CELLULAR BIOENERGETICS REVEALS A MITOCHONDRIAL INSENSITIVE NAD POOL*

Pittelli, Maria; Formentini, Laura; Faraco, Giuseppe; Lapucci, Andrea; Rapizzi, Elena; Cialdai, Francesca; Romano, Giovanni; Moneti, Gloriano; Moroni, Flavio; Chiarugi, Alberto
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.96%
The NAD rescue pathway consists of two enzymatic steps operated by nicotinamide phosphoribosyltransferase (Nampt) and nicotinamide mononucleotide adenylyltransferases. Recently, the potent Nampt inhibitor FK866 has been identified and evaluated in clinical trials against cancer. Yet, how Nampt inhibition affects NAD contents and bioenergetics is in part obscure. It is also unknown whether NAD rescue takes place in mitochondria, and FK866 alters NAD homeostasis within the organelle. Here, we show that FK866-dependent reduction of the NAD contents is paralleled by a concomitant increase of ATP in various cell types, in keeping with ATP utilization for NAD resynthesis. We also show that poly- and mono(ADP-ribose) transferases rather than Sirt-1 are responsible for NAD depletion in HeLa cells exposed to FK866. Mass spectrometry reveals that the drug distributes in the cytosolic and mitochondrial compartment. However, the cytoplasmic but not the mitochondrial NAD pool is reduced upon acute or chronic exposure to the drug. Accordingly, Nampt does not localize within the organelles and their bioenergetics is not affected by the drug. In the mouse, FK866-dependent reduction of NAD contents in various organs is prevented by inhibitors of poly(ADP-ribose) polymerases or the NAD precursor kynurenine. For the first time...

Over-Expressing Mitofusin-2 in Healthy Mature Mammalian Skeletal Muscle Does Not Alter Mitochondrial Bioenergetics

Lally, James S. V.; Herbst, Eric A. F.; Matravadia, Sarthak; Maher, Amy C.; Perry, Christopher G. R.; Ventura-Clapier, Renée; Holloway, Graham P.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 31/01/2013 Português
Relevância na Pesquisa
26.96%
The role of mitofusin-2 (MFN-2) in regulating mitochondrial dynamics has been well-characterized in lower order eukaryotic cell lines through the complete ablation of MFN-2 protein. However, to support the contractile function of mature skeletal muscle, the subcellular architecture and constituent proteins of this tissue differ substantially from simpler cellular organisms. Such differences may also impact the role of MFN-2 in mature mammalian muscle, and it is unclear if minor fluctuations in MFN-2, as observed in response to physiological perturbations, has a functional consequence. Therefore, we have transiently transfected MFN-2 cDNA into rat tibialis anterior muscle to determine the effect of physiolgically relevant increases in MFN-2 protein on mitochondrial bioenergetics. Permeabilized muscle fibres generated from muscle following MFN-2-transfection were used for functional assessments of mitochondrial bioenergetics. In addition, we have further established a novel method for selecting fibre bundles that are positively transfected, and using this approach transient transfection increased MFN-2 protein ∼2.3 fold in selected muscle fibres. However, this did not alter maximal rates of oxygen consumption or the sensitivity for ADP-stimulated respiration. In addition...

Integration of cellular bioenergetics with mitochondrial quality control and autophagy

Hill, Bradford G.; Benavides, Gloria A.; Lancaster, Jack R.; Ballinger, Scott; Dell’Italia, Lou; Zhang, Jianhua; Darley-Usmar, Victor M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/12/2012 Português
Relevância na Pesquisa
26.96%
Bioenergetic dysfunction is emerging as a cornerstone for establishing a framework for understanding the pathophysiology of cardiovascular disease, diabetes, cancer and neurodegeneration. Recent advances in cellular bioenergetics have shown that many cells maintain a substantial bioenergetic reserve capacity, which is a prospective index of “healthy” mitochondrial populations. The bioenergetics of the cell are likely regulated by energy requirements and substrate availability. Additionally, the overall quality of the mitochondrial population and the relative abundance of mitochondria in cells and tissues also impinge on overall bioenergetic capacity and resistance to stress. Because mitochondria are susceptible to damage mediated by reactive oxygen/nitrogen and lipid species, maintaining a “healthy” population of mitochondria through quality control mechanisms appears to be essential for cell survival under conditions of pathological stress. Accumulating evidence suggest that mitophagy is particularly important for preventing amplification of initial oxidative insults, which otherwise would further impair the respiratory chain or promote mutations in mitochondrial DNA (mtDNA). The processes underlying the regulation of mitophagy depend on several factors including the integrity of mtDNA...

Heat Shock Protein 70 Is Necessary to Improve Mitochondrial Bioenergetics and Reverse Diabetic Sensory Neuropathy following KU-32 Therapy

Ma, Jiacheng; Farmer, Kevin L.; Pan, Pan; Urban, Michael J.; Zhao, Huiping; Blagg, Brian S. J.; Dobrowsky, Rick T.
Fonte: The American Society for Pharmacology and Experimental Therapeutics Publicador: The American Society for Pharmacology and Experimental Therapeutics
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.17%
Impaired neuronal mitochondrial bioenergetics contributes to the pathophysiologic progression of diabetic peripheral neuropathy (DPN) and may be a focal point for disease management. We have demonstrated that modulating heat shock protein (Hsp) 90 and Hsp70 with the small-molecule drug KU-32 ameliorates psychosensory, electrophysiologic, morphologic, and bioenergetic deficits of DPN in animal models of type 1 diabetes. The current study used mouse models of type 1 and type 2 diabetes to determine the relationship of changes in sensory neuron mitochondrial bioenergetics to the onset of and recovery from DPN. The onset of DPN showed a tight temporal correlation with a decrease in mitochondrial bioenergetics in a genetic model of type 2 diabetes. In contrast, sensory hypoalgesia developed 10 weeks before the occurrence of significant declines in sensory neuron mitochondrial bioenergetics in the type 1 model. KU-32 therapy improved mitochondrial bioenergetics in both the type 1 and type 2 models, and this tightly correlated with a decrease in DPN. Mechanistically, improved mitochondrial function following KU-32 therapy required Hsp70, since the drug was ineffective in diabetic Hsp70 knockout mice. Our data indicate that changes in mitochondrial bioenergetics may rapidly contribute to nerve dysfunction in type 2 diabetes...

An ortho-carbonyl substituted hydroquinone derivative is an anticancer agent that acts by inhibiting mitochondrial bioenergetics and by inducing G2/M-phase arrest in mammary adenocarcinoma TA3

Ferreira Parker, Jorge Federico; Araya Maturana, Ramiro Juan; Lapier, Michel; Pavani, Mario; Jaña Prado, Fabián; Parra, Eduardo; Martínez Cifuentes, Maximiliano; Pessoa Mahana, Hernán; Maya Arango, Juan Diego; Urra, Félix A.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artículo de revista
Português
Relevância na Pesquisa
36.82%
Artículo de publicación ISI; Tumor cells present a known metabolic reprogramming, which makes them more susceptible for a selective cellular death by modifying its mitochondrial bioenergetics. Anticancer action of the antioxidant 9,10- dihydroxy-4,4-dimethyl-5,8-dihydroanthracen-1(4H)-one (HQ) on mouse mammary adenocarcinoma TA3, and its multiresistant variant TA3-MTXR, were evaluated. HQ decreased the viability of both tumor cells, affecting slightly mammary epithelial cells. This hydroquinone blocked the electron flow through the NADH dehydrogenase (Complex I), leading to ADP-stimulated oxygen consumption inhibition, transmembrane potential dissipation and cellular ATP level decrease,without increasing ROS production. Duroquinol, an electron donor at CoQ level, reversed the decrease of cell viability induced by HQ. Additionally, HQ selectively induced G2/M-phase arrest. Taken together, our results suggest that the bioenergetic dysfunction provoked by HQ is implicated in its anticancer action.