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Carvedilol Inhibits the Exogenous NADH Dehydrogenase in Rat Heart Mitochondria

Oliveira, Paulo J.; Santos, Dario J.; Moreno, António J. M.
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
Português
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There are several reports on the oxidation of external NADH by an exogenous NADH dehydrogenase in the outer leaflet of the inner membrane of rat heart mitochondria. Until now, however, little was known about its physiological role in cellular metabolism. The present work shows that carvedilol ({1-[carbazolyl-(4)-oxy]-3-[2-methoxyphenoxyethyl)amino]-pro- panol-(2)}) is a specific inhibitor of an exogenous NADH dehydrogenase in rat heart mitochondria. Carvedilol does not affect oxygen consumption linked to the oxidation of succinate and internal NADH. It is also demonstrated that the inhibition of exogenous NADH dehydrogenase by carvedilol is accompanied by the inhibition of alkalinization of the external medium. In contrast to the addition of glutamate/malate or succinate, exogenous NADH does not generate a membrane potential in rat heart mitochondria, as observed with a TPP+ electrode. It is also demonstrated that the oxygen consumption linked to NADH oxidation is not due to permeabilized mitochondria, but to actual oxidase activity in the inner membrane. The enzyme has a Km for NADH of 13 [mu]M. Carvedilol is a noncompetitive inhibitor of this external NADH dehydrogenase with a Ki of 15 [mu]M. Carvedilol is the first inhibitor described to this organospecific enzyme. Since this enzyme was demonstrated to play a key role in the cardiotoxicity of anticancer drugs of the anthracycline family (e.g....

A comparative study of plant and animal mitochondria exposed to paraquat reveals that hydrogen peroxide is not related to the observed toxicity

Peixoto, Francisco; Vicente, Joaquim; Madeira, Vítor M. C.
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
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Rat liver mitochondria are much more susceptible to protein oxidation induced by paraquat than plant mitochondria. The unsaturated index and the peroxidizability index are higher in rat than in potato tuber. The levels of superoxide dismutase and glutathione reductase are concurrent with the different sensitivities to paraquat, with higher activities in plant mitochondria. However, glutathione peroxidase and catalase activities are higher in rat mitochondria. Paraquat (10 mM) inhibited all the enzymatic activities; excluding catalase all the other activities were inhibited to a similar degree. The differential sensitivities of plant and animal mitochondria to paraquat correlate with fatty acid composition of mitochondrial lipids and a similar correlation was also established for some antioxidant enzymes. At the mitochondrial level, H2O2 is not a major factor of paraquat toxicity since rat liver mitochondria which exhibit higher activities of glutathione peroxidase and catalase are however more susceptible to paraquat.; http://www.sciencedirect.com/science/article/B6TCP-4C47JVD-3/1/ef7e44af2ded145614d9b786098438ce

Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria

Cunha-Oliveira, Teresa; Silva, Lisbeth; Silva, Ana Maria; Moreno, António J.; Oliveira, Catarina R.; Santos, Maria S.
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica
Português
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Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented. Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction. In this work, we compared the effects of cocaine and/or morphine on the bioenergetics of isolated brain and liver mitochondria, to understand their specific effects in each tissue. Upon energization with complex I substrates, cocaine decreased state-3 respiration in brain (but not in liver) mitochondria and decreased uncoupled respiration and mitochondrial potential in both tissues, through a direct effect on complex I. Morphine presented only slight effects on brain and liver mitochondria, and the combination cocaine+morphine had similar effects to cocaine alone, except for a greater decrease in state-3 respiration. Brain and liver mitochondrial respirations were differentially affected, and liver mitochondria were more prone to proton leak caused by the drugs or their combination. This was possibly related with a different dependence on complex I in mitochondrial populations from these tissues. In summary...

Mitochondria and mammalian reproduction

Ramalho-Santos, J.; Amaral, Sandra
Fonte: Elsevier Ireland Ltd. Publicador: Elsevier Ireland Ltd.
Tipo: Artigo de Revista Científica
Português
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Mitochondria are cellular organelles with crucial roles in ATP synthesis, metabolic integration, reactive oxygen species (ROS) synthesis and management, the regulation of apoptosis (namely via the intrinsic pathway), among many others. Additionally, mitochondria in different organs or cell types may have distinct properties that can decisively influence functional analysis. In terms of the importance of mitochondria in mammalian reproduction, and although there are species-specific differences, these aspects involve both energetic considerations for gametogenesis and fertilization, control of apoptosis to ensure the proper production of viable gametes, and ROS signaling, as well as other emerging aspects. Crucially, mitochondria are the starting point for steroid hormone biosynthesis, given that the conversion of cholesterol to pregnenolone (a common precursor for all steroid hormones) takes place via the activity of the cytochrome P450 side-chain cleavage enzyme (P450scc) on the inner mitochondrial membrane. Furthermore, mitochondrial activity in reproduction has to be considered in accordance with the very distinct strategies for gamete production in the male and female. These include distinct gonad morpho-physiologies, different types of steroids that are more prevalent (testosterone...

UCP2 and ANT differently modulate proton-leak in brain mitochondria of long-term hyperglycemic and recurrent hypoglycemic rats

Cardoso, Susana; Santos, M. S.; Moreno, A. J. M.; Moreira, Paula I.
Fonte: Springer Science Publicador: Springer Science
Tipo: Artigo de Revista Científica
Português
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A growing body of evidence suggests that mitochondrial proton-leak functions as a regulator of reactive oxygen species production and its modulation may limit oxidative injury to tissues. The main purpose of this work was to characterize the proton-leak of brain cortical mitochondria from long-term hyperglycemic and insulininduced recurrent hypoglycemic rats through the modulation of the uncoupling protein 2 (UCP2) and adenine nucleotide translocator (ANT). Streptozotocin-induced diabetic rats were treated subcutaneously with twice-daily insulin injections during 2 weeks to induce the hypoglycemic episodes. No differences in the basal proton-leak, UCP2 and ANT protein levels were observed between the experimental groups. Mitochondria from recurrent hypoglycemic rats presented a decrease in proton-leak in the presence of GDP, a specific UCP2 inhibitor, while an increase in proton-leak was observed in the presence of linoleic acid, a proton-leak activator, this effect being reverted by the simultaneous addition of GDP. Mitochondria from longterm hyperglycemic rats showed an enhanced susceptibility to ANT modulation as demonstrated by the complete inhibition of basal and linoleic acid-induced proton-leak caused by the ANT specific inhibitor carboxyatractyloside. Our results show that recurrent-hypoglycemia renders mitochondria more susceptible to UCPs modulation while the protonleak of long-term hyperglycemic rats is mainly modulated by ANT...

Characterization of the stimulus for reactive oxygen species generation in calcium-overloaded mitochondria

RODRIGUES, Fernando P.; PESTANA, Cezar R.; SANTOS, Guilherme A. Dos; PARDO-ANDREU, Gilberto L.; SANTOS, Antonio C.; UYEMURA, Sergio A.; ALBERICI, Luciane C.; CURTI, Carlos
Fonte: MANEY PUBLISHING Publicador: MANEY PUBLISHING
Tipo: Artigo de Revista Científica
Português
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We have used two different probes with distinct detection properties, dichlorodihydrofluorescein diacetate and Amplex Red/horseradish peroxidase, as well as different respiratory substrates and electron transport chain inhibitors, to characterize the reactive oxygen species (ROS) generation by the respiratory chain in calcium-overloaded mitochondria. Regardless of the respiratory substrate, calcium stimulated the mitochondrial generation of ROS, which were released at both the mitochondrial-matrix side and the extramitochondrial space, in a way insensitive to the mitochondrial permeability transition pores inhibitor cyclosporine A. In glutamate/malate-energized mitochondria, inhibition at complex I or complex III (ubiquinone cycle) similarly modulated ROS generation at either mitochondrial-matrix side or extramitochondrial space; this also occurred when the backflow of electrons to complex I in succinate-energized mitochondria was inhibited. On the other hand, in succinate-energized mitochondria the modulation of ROS generation at mitochondrial-matrix side or extra-mitochondrial space depends on the site of complex III which was inhibited. These results allow a straight comparison between the effects of different respiratory substrates and electron transport chain inhibitors on ROS generation at either mitochondrial-matrix side or extra-mitochondrial space in calcium-overloaded mitochondria.; FAPESP; CAPES; CNPq...

Antioxidant activity of flavonoids in isolated mitochondria

DORTA, Daniel J.; PIGOSO, Acacio A.; MINGATTO, Fabio E.; RODRIGUES, Tiago; PESTANA, Cezar R.; UYEMURA, Sergio A.; SANTOS, Antonio C.; CURTI, Carlos
Fonte: JOHN WILEY & SONS LTD Publicador: JOHN WILEY & SONS LTD
Tipo: Artigo de Revista Científica
Português
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Mitochondria are important intracellular sources and targets of reactive oxygen species (ROS), while flavonoids, a large group of secondary plant metabolites, are important antioxidants. Following our previous study on the energetics of mitochondria exposed to the flavonoids quercetin, taxifolin, catechin and galangin, the present work addressed the antioxidant activity of these compounds (1-50 mu mol/L) on Fe2+/citrate-mediated membrane lipid peroxidation (LPO) in isolated rat liver mitochondria, running in parallel studies of their antioxidant activity in non-organelle systems. Only quercetin inhibited the respiratory chain of mitochondria and only galangin caused uncoupling. Quercetin and galangin were far more potent than taxifolin and catechin in affording protection against LPO (IC50 = 1.23 +/- 0.27 and 2.39 +/- 0.79 mu mol/L, respectively), although only quercetin was an effective scavenger of both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals. These results, together with the previous study, suggest that the 2,3-double bond in conjugation with the 4-oxo function in the flavonoid structure are major determinants of the antioxidant activity of flavonoids in mitochondria, the presence of an o-di-OH structure on the B-ring...

Characterization of Rubus fruticosus mitochondria and salicylic acid inhibition of reactive oxygen species generation at Complex III/Q cycle: potential implications for hypersensitive response in plants

SOUZA, Wagner Rodrigo de; VESSECCHI, Ricardo; DORTA, Daniel Junqueira; UYEMURA, Sergio Akira; CURTI, Carlos; VARGAS-RECHIA, Carem Gledes
Fonte: SPRINGER/PLENUM PUBLISHERS Publicador: SPRINGER/PLENUM PUBLISHERS
Tipo: Artigo de Revista Científica
Português
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In addition to adenosine triphosphate (ATP) production, mitochondria have been implicated in the regulation of several physiological responses in plants, such as programmed cell death (PCD) activation. Salicylic acid (SA) and reactive oxygen species (ROS) are essential signaling molecules involved in such physiological responses; however, the mechanisms by which they act remain unknown. In non-photosynthesizing tissues, mitochondria appear to serve as the main source of ROS generation. Evidence suggests that SA and ROS could regulate plant PCD through a synergistic mechanism that involves mitochondria. Herein, we isolate and characterize the mitochondria from non-photosynthesizing cell suspension cultures of Rubus fruticosus. Furthermore, we assess the primary site of ROS generation and the effects of SA on isolated organelles. Mitochondrial Complex III was found to be the major source of ROS generation in this model. In addition, we discovered that SA inhibits the electron transport chain by inactivating the semiquinone radical during the Q cycle. Computational analyses confirmed the experimental data, and a mechanism for this action is proposed.; CAPES; CNPq; FAPESP

Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

ANDREU, G. L. Pardo; INADA, N. M.; VERCESI, A. E.; CURTI, C.
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
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One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21 +/- A 4 to 130 +/- A 7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H(+) leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria.; FAPESP, Brasil; ""Red de Macrouniversidades de America Latina y el Caribe""

Relationship Between Expression of Voltage-Dependent Anion Channel (VDAC) Isoforms and Type of Hexokinase Binding Sites on Brain Mitochondria

POLETI, Mirele Daiana; TESCH, Andrea Cristina; CREPALDI, Carla Rossini; SOUZA, Gustavo Henrique Martins Ferreira; EBERLIN, Marcos Nogueira; CESAR, Marcelo de Cerqueira
Fonte: HUMANA PRESS INC Publicador: HUMANA PRESS INC
Tipo: Artigo de Revista Científica
Português
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36.56%
Voltage-dependent anion channels (VDAC) are pore-forming proteins found in the outer mitochondrial membrane of eukaryotes. VDACs are known to play an essential role in cellular metabolism and in early stages of apoptosis. In mammals, three VDAC isoforms have been identified. A proteomic approach was exploited to study the expression of VDAC isoforms in rat, bovine, and chicken brain mitochondria. Given the importance of mitochondrially bound hexokinase in regulation of aerobic glycolysis in brain, we studied the possibility that differences in the relative expression of VDAC isoforms may be a factor in determining the species-dependent ratio of type A/type B hexokinase binding sites on brain mitochondria. The spots were characterized, and the signal intensities among spots were compared. VDAC1 was the most abundantly expressed of the three isoforms. Moreover the expression of VDAC1 plus VDAC2 was significantly higher in bovine than in rat brain. Chicken brain mitochondria showed the highest VDAC1 expression and the lowest of VDAC2. Bovine brain mitochondria had the highest VDAC2 levels. We concluded that the nature of hexokinase binding site is not determined by the expression of a single VDAC isoform.; FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[2004/03170-5]

Eficiência fotodinâmica dos fenotiazínicos em mitocôndrias e células tumorais; Photodynamic efficiency of phenotiazinic compounds into mitochondria and tumor cells

Gabrielli, Dino Santesso
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 14/06/2007 Português
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O mecanismo de ação de fotossensibilizadores (FS) fenotiazínicos (azul de metileno - AM, tionina - TIO e azure B - AB) foi estudado em mitocôndrias e células Hela, e a dosimetria de AM em células HL60. Foi observado que a ligação de AM em mitocôndrias é dependente da concentração de mitocôndrias, concentração de AM e do potencial de membrana mitocondrial (Δ Ψ). A geração de oxigênio singlete a partir de AM é influenciada pelo Δ Ψ, sendo aproximadamente o dobro em mitocôndrias desacopladas. Essa variação se deve a influência do Δ Ψ sobre a relação dímero/monômero (D/M) do AM. A ligação de AM também é reduzida pela metade em mitocôndrias desacopladas. Esses efeitos não foram observados para os outros fotossensibilizadores, embora tenham a mesma carga e estrutura semelhante. Isso indica um efeito diferencial do Δ Ψ sobre o AM. Foi observada a toxicidade desses FSs em células Hela. Sem irradiação, apenas AB se mostrou tóxico. Em amostras irradiadas, AB e AM se mostraram tóxicos. Todos os FSs mostraram capacidade de produzir núcleos sub-diplóides, típicos de apoptose, com a maior eficiência sendo do AB. Em relação a toxicidade no escuro e claro...

Abamectin affects the bioenergetics of liver mitochondria: A potential mechanism of hepatotoxicity

Castanha Zanoli, Juliana C.; Maioli, Marcos A.; Medeiros, Hyllana C. D.; Mingatto, Fábio Erminio
Fonte: Pergamon-Elsevier B.V. Ltd Publicador: Pergamon-Elsevier B.V. Ltd
Tipo: Artigo de Revista Científica Formato: 51-56
Português
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Abamectin (ABA) is a macrocyclic lactone of the avermectin family used worldwide as an antiparasitic agent in farm animals and pets and as the active ingredient of insecticides and nematicides. In this study, the effects of abamectin on the bioenergetics of mitochondria isolated from rat liver were evaluated. Mitochondria are responsible for converting the energy released by electron transport and stored as the binding energy molecule ATP. Xenobiotics that interfere with its synthesis or utilization can be acutely or chronically toxic. Abamectin (5-251 mu M) caused concentration-dependent inhibition of the respiratory chain without affecting the membrane potential or the activity of enzymes NADH dehydrogenase or succinate dehydrogenase. This behavior is similar to oligomycin and carboxyatractyloside and suggests direct action on F0F1-ATPase and/or the adenine nucleotide translocator (ANT). ABA more pronouncedly inhibited ATPase phosphohydrolase activity in intact, uncoupled mitochondria than in freeze-thawed disrupted mitochondria. ADP-stimulated depolarization of the mitochondrial membrane potential was also inhibited by ABA. Our results indicate that ABA interacts more specifically with the ANT...

Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

ANDREU, G. L. Pardo; INADA, N. M.; VERCESI, A. E.; CURTI, C.
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.6%
One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21 +/- A 4 to 130 +/- A 7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H(+) leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria.; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Relationship Between Expression of Voltage-Dependent Anion Channel (VDAC) Isoforms and Type of Hexokinase Binding Sites on Brain Mitochondria

POLETI, Mirele Daiana; TESCH, Andrea Cristina; CREPALDI, Carla Rossini; SOUZA, Gustavo Henrique Martins Ferreira; EBERLIN, Marcos Nogueira; CESAR, Marcelo de Cerqueira
Fonte: HUMANA PRESS INC Publicador: HUMANA PRESS INC
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.56%
Voltage-dependent anion channels (VDAC) are pore-forming proteins found in the outer mitochondrial membrane of eukaryotes. VDACs are known to play an essential role in cellular metabolism and in early stages of apoptosis. In mammals, three VDAC isoforms have been identified. A proteomic approach was exploited to study the expression of VDAC isoforms in rat, bovine, and chicken brain mitochondria. Given the importance of mitochondrially bound hexokinase in regulation of aerobic glycolysis in brain, we studied the possibility that differences in the relative expression of VDAC isoforms may be a factor in determining the species-dependent ratio of type A/type B hexokinase binding sites on brain mitochondria. The spots were characterized, and the signal intensities among spots were compared. VDAC1 was the most abundantly expressed of the three isoforms. Moreover the expression of VDAC1 plus VDAC2 was significantly higher in bovine than in rat brain. Chicken brain mitochondria showed the highest VDAC1 expression and the lowest of VDAC2. Bovine brain mitochondria had the highest VDAC2 levels. We concluded that the nature of hexokinase binding site is not determined by the expression of a single VDAC isoform.; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphological abnormalities in mitochondria of the skin of patients with sporadic amyotrophic lateral sclerosis

Rodríguez,Gabriel E.; González,Deniselle M. Claudia; Monachelli,Gisella M. Gargiulo; Costa,Juan J. López; Nicola,Alejandro F. de; Sica,Roberto E. P.
Fonte: Academia Brasileira de Neurologia - ABNEURO Publicador: Academia Brasileira de Neurologia - ABNEURO
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2012 Português
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36.56%
OBJECTIVES: Mitochondrial dysfunction has been reported in the central nervous system, hepatocytes and peripheral blood lymphocytes from patients with sporadic amyotrophic lateral sclerosis (SALS). However, the status of skin mitochondria has not been reported, in spite of the fact that SALS patients present skin abnormalities. The objective of the present study was to compare mitochondrial ultrastructural parameters in keratinocytes from patients with SALS and healthy controls. METHODS: Our study was based on the analysis of 112 skin mitochondria from 5 SALS patients and 99 organelles from 4 control subjects by electron microscopy. RESULTS: Computerized image analysis showed that mitochondrial major axis length, area and perimeter of the organelle were significantly smaller in SALS respect of healthy control subjects. Morphologically, SALS mitochondria presented cristolysis and breakage of the outer membrane. CONCLUSIONS: Mitochondrial dysfunction in the skin may possibly reflect changes occurring in mitochondria of the central nervous system. The analysis of mitochondrial morphology in this tissue may be of value to follow disease progression and, eventually, the effectiveness of current therapies for SALS.

Improved method for isolation of coupled mitochondria of Araucaria angustifolia (Bert.) O. Kuntze

Mariano,André Bellin; Kovalhuk,Leonardo; Valente,Caroline; Maurer-Menestrina,Juliana; Pereira-Netto,Adaucto Bellarmino; Guerra,Miguel Pedro; Carnieri,Eva Gunilla Skare
Fonte: Instituto de Tecnologia do Paraná - Tecpar Publicador: Instituto de Tecnologia do Paraná - Tecpar
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2004 Português
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A method for the isolation of coupled mitochondria from the callus of Araucaria angustifolia is described for the first time. Mitochondria were isolated from embryogenic callus of A. angustifolia. They were metabolically active, able to sustain oxidative phosphorylation as shown by respiratory control ratio values, which were about 2.4 when respiring on succinate as substrate. Oxygen uptake experiments, using freeze-thawed disrupted mitochondria, showed the presence of alternative rotenone-insensitive NAD(P)H dehydrogenases, which were stimulated by Ca2+. The procedure now described for the isolation of A. angustifolia mitochondria is an important new tool, allowing the investigation of mitochondrial bioenergetics and metabolism and physiology of plants.

c-FLIPL localizes at the Endoplasmic Reticulum and Mitochondria-associated membranes and regulates organelle morphology and ER-mitochondria crosstalk

MARINI, ELETTRA SARA
Fonte: La Sapienza Universidade de Roma Publicador: La Sapienza Universidade de Roma
Tipo: Tese de Doutorado
Português
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Cellular FLICE-inhibitory proteins (c-FLIPs) regulate Death Receptor (DR)-induced apoptotic as well as non-apoptotic pathways, by modulating caspase-8 activation. Here we showed that the long isoform of c-FLIP unexpectedly controls the Endoplasmic Reticulum (ER) morphology and the physical and functional crosstalk between ER and mitochondria. Besides its previously described cytosolic localization, we observed that c-FLIPL is also retrieved at the ER and Mitochondria-associated membranes (MAMs), ER subdomains involved in the ER-to-mitochondria Ca2+ transport, lipid metabolism and ER stress-induced apoptosis. We demonstrated that the ablation of c-FLIPL in mouse embryonic fibroblasts (MEFs) specifically alters ER morphology, inducing ER-sheets proliferation and altering the luminal contiguity of this organelle. Re-introduction of c-FLIPL in c-FLIP-/- cells partially recovers these structural defects, therefore confirming the role of c-FLIPL in modulation of ER morphology. In agreement, we also reported that c-FLIP-/- MEFs show reduced expression of the ER shaping protein reticulon4 (RTN4), that is mainly known as regulator of ER biogenesis and dynamics. Furthermore, we observed that c-FLIPL ablation loosens ER-mitochondria juxtaposition. We demonstrated that functionally...

Morphological differentiation of mitochondria in the early chick embryo: a stereological analysis

Paz, P. de; Zapata, A.; Renau-Piqueras, J.; Miragal, F.
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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The morphological evolution of mitochondria in three cell types of chick embryo in neurulation was analyzed by stereological methods. Mitochondria, showing a random distribution, were characterized by moderate electron-dense matrices and normal cristae. The numerical density of mitochondria significantly increased in the neuroectoderm and epiblastic cells while their volume density remained unchanged. The mitochondria in mesoderm cells were ellipsoidal (axial ratio 2:l) at stages 5 and 8 although they underwent an elongation in neuroectoderm and epiblastic cells (axial ratio from 2: 1 to 1.6: 1). The individual size of "average mitochondria" in the mesoderm cells was smaller than in other cell types. The total V/S (volume/surface) ratio of mitochondria decreased during neurulation. These morphological changes have been discussed emphasizing the possible metabolical role of mitochondria during morphogenesis

Heart mitochondria in rats submitted to chronic hypoxia

Cervós-Navarro, J.; Kunas, R.Ch.; Sampaolo, S.; Mansmann, U.
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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The effect of prolonged exposure to normobaric hypoxia on the mitochondria of myocard of rats exposed for several weeks to 8 and 7% O2 has been morphometrically evaluated. Twelve male Wistar rats housed in Nalgene cages (2 per cage) with a batch of six cages placed in plexiglass chambers were maintained in air/N2 mixtures containing different concentrations of 02. Six animals kept in similar cages under normoxia served as controls. When at day 60 the FIOZ was reduced to 8%, the weight increase stagnated and after the 81st test day, on which the hypoxic animals were subdivided into 8% and 7% groups the weight curve showed a decrease in the mean body weight for both groups. The arrest and the following loss of weight beyond the 85th day may be interpreted as the expression of a limit reached in the compensation capacity. In the 8%-group the shape of the mitochondria varied more markedly often with budding and furrowing of the surface. In the 7%-group bizarre shapes and wide variations in size with a decided shift towards larger mitochondria were noteworthy. While rats kept under 8% oxygen exhibited a numerical increase in myocardial mitochondria compared to controls, the mitochondria of the 7%-group were numerically reduced. The results suggest that hypoxia of 8% oxygen is compensatable...

Mitochondria as a Target of Benzo[a]pyrene Toxicity in a PAH-adapted and Naive Population of the Atlantic Killifish (Fundulus Heteroclitus)

Jung, Dawoon
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação Formato: 2406157 bytes; application/pdf
Publicado em //2009 Português
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Polycyclic aromatic hydrocarbons (PAHs) are important contaminants that are found in increasing amounts in aquatic ecosystems. One of the sites that that is contaminated by extremely high levels of PAHs is the Atlantic Wood Industries Superfund Site on the Elizabeth River, VA. The Atlantic killifish (Fundulus heteroclitus) from this site exhibit increased levels of antioxidants, increased sensitivity to hypoxia, and increased expression of enzymes involved in glycolytic metabolism, suggesting that exposure to PAHs in the environment may induce changes in mitochondrial function and energy metabolism. Normal mitochondrial activity is crucial to an organism's survival. Therefore, gaining a better understanding of how mitochondria are affected by environmental contaminants such as PAHs is a pressing research objective. As a first step in understanding changes in cellular bioenergetics of aquatic organisms in response to PAHs, this research focused on the effect of benzo[a]pyrene (BaP), a representative PAH, on mitochondria the killifish model and on comparison of the mitochondria of the PAH-adapted killifish from the Elizabeth River Superfund Site to reference site fish. In order to assess the extent of mitochondrial DNA damage in the killifish...