Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Mitochondrial Permeability Transition And Oxidative Stress

Mitochondrial permeability transition (MPT) is a non-selective inner membrane permeabilization that may precede necrotic and apoptotic cell death. Although this process has a specific inhibitor, cyclosporin A, little is known about the nature of the proteinaceous pore that results in MPT. Here, we review data indicating that MPT is not a consequence of the opening of a pre-formed pore, but the consequence of oxidative damage to pre-existing membrane proteins. © 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.4951-21215Liu, X., Kim, C.N., Yang, J., Jemmerson, R., Wang, X., (1996) Cell, 86, pp. 147-157Susin, S.A., Zamzami, N., Castedo, M., Hirsch, T., Marchetti, P., Macho, A., Daugas, E., Kroemer, G., (1996) J. Exp. Med., 184, pp. 1331-1341Green, D.R., Reed, J.C., (1998) Science, 281, pp. 1309-1312Skulachev, V.P., (1998) FEBS Lett., 423, pp. 275-280Kroemer, G., (1999) Biochem. Soc. Symp., 66, pp. 1-15Zoratti, M., Szabò, I., (1995) Biochim. Biophys. Acta, 1241, pp. 139-176Kowaltowski, A.J., Vercesi, A.E., (1999) Free Radic. Biol. Med., 26, pp. 463-471Castilho, R.F., Kowaltowski, A.J., Vercesi, A.E., (1996) J. Bioenerg. Biomembr., 28, pp. 523-529Fagian, M.M., Pereira-da-Silva, L., Martins, I.S., Vercesi, A.E., (1990) J. Biol. Chem., 265, pp. 19955-19960Vercesi, A.E., (1984) Biochem. Biophys. Res. Commun., 119, pp. 305-310Brustovetsky, N., Klingenberg, M., (1996) Biochemistry, 35, pp. 8483-8488Brdiczka, D., Beutner, G., Ruck, A., Dolder, M., Wallimann, T., (1998) Biofactors, 8, pp. 235-242Halestrap, A.P., (1999) Biochem. Soc. Symp., 66, pp. 181-203Lehninger, A.L., Vercesi, A.E., Bababunmi, E.A., (1978) Proc. Natl. Acad. Sci. USA, 75, pp. 1690-1694Hunter, D.R., Haworth, R.A., (1979) Arch. Biochem. Biophys., 195, pp. 453-459Lotscher, H.R., Winterhalter, K.H., Carafoli, E., Richter, C., (1980) J. Biol. Chem., 255, pp. 9325-9330Jurkowitz, M.S., Geisbuhler, T., Jung, D.W., Brierley, G.P., (1983) Arch. Biochem. Biophys., 223, pp. 120-128Vercesi, A.E., (1987) Arch. Biochem. Biophys., 252, pp. 171-178Byrne, A.M., Lemasters, J.J., Nieminen, A.L., (1999) Hepatology, 29, pp. 1523-1531Zago, E.B., Castilho, R.F., Vercesi, A.E., (2000) FEBS Lett., 478, pp. 29-33Bernardes, C.F., Meyer-Fernandes, J.R., Basseres, D.S., Castilho, R.F., Vercesi, A.E., (1994) Biochim. Biophys. Acta, 1188, pp. 93-100Hoek, J.B., Rydstrom, J., (1988) Biochem. J., 254, pp. 1-10Kowaltowski, A.J., Vercesi, A.E., (2000) Mitochondria in Pathogenesis, , (Lemasters, J.J. and Nieminen A.-L., Eds.), Plenum, New York, in pressGardner, P.R., Fridovich, I., (1991) J. Biol. Chem., 266, pp. 19328-19333Skulachev, V.P., (1997) Biosci. Rep., 17, pp. 347-366Peng, C.F., Straub, K.D., Kane, J.J., Murphy, M.L., Wadkins, C.L., (1977) Biochim. Biophys. Acta, 462, pp. 403-413Bernardi, P., Azzone, G.F., (1983) Eur. J. Biochem., 134, pp. 377-383Catisti, R., Vercesi, A.E., (1999) FEBS Lett., 464, pp. 97-101Kowaltowski, A.J., Vercesi, A.E., Fiskum, G., (2000) Cell Death Differ., 7, pp. 903-910Korshunov, S.S., Skulachev, V.P., Starkov, A.A., (1997) FEBS Lett., 416, pp. 15-18Skulachev, V.P., (1998) Biochim. Biophys. Acta, 1363, pp. 100-124Le Quoc, D., Le Quoc, K., Gaudemer, Y., (1976) Biochem. Biophys. Res. Commun., 68, pp. 106-113Harris, E.J., Baum, H., (1980) Biochem. J., 186, pp. 725-732Vercesi, A.E., Ferraz, V.L., Macedo, D.V., Fiskum, G., (1988) Biochem. Biophys. Res. Commun., 154, pp. 934-941Valle, V.G., Fagian, M.M., Parentoni, L.S., Meinicke, A.R., Vercesi, A.E., (1993) Arch. Biochem. Biophys., 307, pp. 1-7Siliprandi, D., Scutari, G., Zoccarato, F., Siliprandi, N., (1974) FEBS Lett., 42, pp. 197-199Lenartowicz, E., Bernardi, P., Azzone, G.F., (1991) J. Bioenerg. Biomembr., 23, pp. 679-688Costantini, P., Chernyak, B.V., Petronilli, V., Bernardi, P., (1996) J. Biol. Chem., 271, pp. 6746-6751Castilho, R.F., Kowaltowski, A.J., Meinicke, A.R., Bechara, E.J., Vercesi, A.E., (1995) Free Radic. Biol. Med., 18, pp. 479-486Costantini, P., Belzacq, A.S., Vieira, H.L., Larochette, N., De Pablo, M.A., Zamzami, N., Susin, S.A., Kroemer, G., (2000) Oncogene, 19, pp. 307-314Kowaltowski, A.J., Castilho, R.F., Grijalba, M.T., Bechara, E.J., Vercesi, A.E., (1996) J. Biol. Chem., 271, pp. 2929-2934Kowaltowski, A.J., Castilho, R.F., Vercesi, A.E., (1996) FEBS Lett., 378, pp. 150-152Kowaltowski, A.J., Netto, L.E., Vercesi, A.E., (1998) J. Biol. Chem., 273, pp. 12766-12769Kowaltowski, A.J., Castilho, R.F., Vercesi, A.E., (1995) Am. J. Physiol., 269, pp. C141-C147Scorrano, L., Petronilli, V., Bernardi, P., (1997) J. Biol. Chem., 272, pp. 12295-12299Kuzminova, A.E., Zhuravlyova, A.V., Vyssokikh, M.Yu., Zorova, L.D., Krasnikov, B.F., Zorov, D.B., (1998) FEBS Lett., 434, pp. 313-316Frei, B., Winterhalter, K.H., Richter, C., (1985) J. Biol. Chem., 260, pp. 7394-7401Hermes-Lima, M., Valle, V.G., Vercesi, A.E., Bechara, E.J., (1991) Biochim. Biophys. Acta, 1056, pp. 57-63Packer, M.A., Murphy, M.P., (1995) Eur. J. Biochem., 234, pp. 231-239Gadelha, F.R., Thomson, L., Fagian, M.M., Costa, A.D.T., Radi, R., Vercesi, A.E., (1997) Arch. Biochem. Biophys., 345, pp. 243-250Grijalba, M.T., Vercesi, A.E., Schreier, S., (1999) Biochemistry, 38, pp. 13279-13287Indig, G.L., Campa, A., Bechara, E.J.H., Cilento, G., (1988) Photochem. Photobiol., 48, pp. 719-723Zhang, P., Liu, B., Kang, S.W., Seo, M.S., Rhee, S.G., Obeid, L.M., (1997) J. Biol. Chem., 272, pp. 30615-30618Backway, K.L., McCulloch, E.A., Chow, S., Hedley, D.W., (1997) Cancer Res., 57, pp. 2446-2451Quillet-Mary, A., Jaffrezou, J.P., Mansat, V., Bordier, C., Naval, J., Laurent, G., (1997) J. Biol. Chem., 272, pp. 21388-21395Murakami, K., Kondo, T., Kawase, M., Li, Y., Sato, S., Chen, S.F., Chan, P.H., (1998) J. Neurosci., 18, pp. 205-213Fujimura, M., Morita-Fujimura, Y., Noshita, N., Sugawara, T., Kawase, M., Chan, P.H., (2000) J. Neurosci., 20, pp. 2817-2824Voehringer, D.W., Hirschberg, D.L., Xiao, J., Lu, Q., Roederer, M., Lock, C.B., Herzenberg, L.A., Herzenberg, L.A., (2000) Proc. Natl. Acad. Sci. USA, 97, pp. 2680-2685Petersen, A., Castilho, R.F., Hansson, O., Wieloch, T., Brundin, P., (2000) Brain Res., 857, pp. 20-29Nieminen, A.L., Byrne, A.M., Herman, B., Lemasters, J.J., (1997) Am. J. Physiol., 272, pp. C1286-C1294Dhanbhoora, C.M., Babson, J.R., (1992) Arch. Biochem. Biophys., 293, pp. 130-139Ghibelli, L., Coppola, S., Fanelli, C., Rotilio, G., Civitareale, P., Scovassi, A.I., Ciriolo, M.R., (1999) FASEB J., 13, pp. 2031-2036Yang, C.F., Shen, H.M., Ong, C.N., (2000) Arch. Biochem. Biophys., 380, pp. 319-330Skulachev, V.P., (1999) Mol. Asp. Med., 20, pp. 139-18

Ca2+-induced Mitochondrial Membrane Permeabilization: Role Of Coenzyme Q Redox State

Rotenone-poisoned rat liver mitochondria energized by succinate addition, after a 5-min period of preincubation in presence of 10 μM Ca2+, produce H2O2 at much faster rates, undergo extensive swelling, and are not able to retain the membrane potential and accumulated Ca2+. Similar results were obtained when a suspension of rat liver mitochondria preincubated in anaerobic medium for 5 min was reoxygenated. The addition of either ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid, ruthenium red, catalase, or dithiothreitol, just before succinate or O2 addition, prevented mitochondrial swelling, indicating the involvement of Ca2+, reactive oxygen species, and oxidation of membrane protein thiols in this process of membrane permeabilization. Inhibition of mitochondrial swelling by cyclosporin A suggests that the membrane alterations observed under these experimental conditions are related to opening of the permeability transition pore. The presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone, which prevents Ca2+ cycling across the membrane, did not inhibit mitochondrial swelling when Ca2+ influx into the mitochondrial matrix was driven by a high Ca2+ gradient. When rotenone plus antimycin A-poisoned mitochondria were energized by N,N,N',N'-tetramethyl-p-phenylenediamine, which reduces respiratory chain complex IV, mitochondrial swelling did not occur, unless succinate, which reduces coenzyme Q, was also added. It is concluded that reduced coenzyme Q is the electron source for oxygen radical production during Ca2+-stimulated oxidative damage of mitochondria.2691 38-1C141C14

High Susceptibility Of Activated Lymphocytes To Oxidative Stress-induced Cell Death

The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to iert-butyl hydroperoxide (t-BOOH)-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca 2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.801137148ABE, K., SAITO, H., Characterization of t-butyl hydroperoxide toxicity in cultured rat cortical neurones and astrocytes (1998) Pharmacol Toxicol, 83, pp. 40-46ARNOLD, R., BRENNER, D., BECKER, M., FREY, C.R., KRAMMER, P.H., How T lymphocytes switch between life and death (2006) Eur J Immunol, 36, pp. 1654-1658BARTESAGHI, S., TRUJILLO, M., DENICOLA, A., FOLKES, L., WARDMAN, P., RADI, R., Reactions of desferrioxamine with peroxynitrite-derived carbonate and nitrogen dioxide radicals (2004) Free Radic Biol Med, 36, pp. 471-483BARTOLI, G.M., PICCIONI, E., AGOSTARA, G., CALVIELLO, G., PALOZZA, P., Different mechanisms of tert-butyl hydroperoxide-induced lethal injury in normal and tumor thymocytes (1994) Arch Biochem Biophys, 312, pp. 81-87BERNARDES, C.F., PEREIRA, DA SILVA, L., VERCESI, A.E., t-Butylhydroperoxide-induced Ca2+ efflux from liver mitochondria in the presence of physiological concentrations of Mg2+ and ATP (1986) Biochim Biophys Acta, 850, pp. 41-48BOYUM, A., Isolation of lymphocytes, granulocytes and macrophages (1976) Scand J Immunol, (SUPPL. 5), pp. 9-15BRUMATTI, G., WEINLICH, R., CHEHAB, C.F., YON, M., AMARANTE-MENDES, G.P., Comparison of the anti-apoptotic effects of Bcr-Abl, Bcl-2 and Bcl-x(L) following diverse apoptogenic stimuli (2003) FEBS Lett, 541, pp. 57-63BUTTKE, T.M., SANDSTROM, P.A., Redox regulation of programmed cell death in lymphocytes (1995) Free Radic Res, 22, pp. 389-397CAMPOS, C.B., DEGASPERI, G.R., PACIFICO, D.S., ALBERICI, L.C., CARREIRA, R.S., GUIMARÃES, F., CASTILHO, R.F., VERCESI, A.E., Ibuprofen-induced Walker 256 tumor cell death: Cytochrome c release from functional mitochondria and enhancement by calcineurin inhibition (2004) Biochem Pharmacol, 68, pp. 2197-2206CASTILHO, R.F., KOWALTOWSKI, A.J., MEINICKE, A.R., BECHARA, E.J., VERCESI, A.E., Permeabilization of the inner mitochondrial membrane by Ca2+ ions is stimulated by t-butyl hydroperoxide and mediated by reactive oxygen species generated by mitochondria (1995) Free Radic Biol Med, 18, pp. 479-486CONKLIN, K.A., Chemotherapy-associated oxidative stress: Impact on chemotherapeutic effectiveness (2004) Integr Cancer Ther, 3, pp. 294-300CROMPTON, M., ELLINGER, H., COSTI, A., Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress (1988) Biochem J, 255, pp. 357-360CROMPTON, M., The mitochondrial permeability transition pore and its role in cell death (1999) Biochem J, 341, pp. 233-249DALY, M.J., YOUNG, R.J., BRITNELL, S.L., NAYLER, W.G., The role of calcium in the toxic effects of tert-butyl hydroperoxide on adult rat cardiac myocytes (1991) J Mol Cell Cardiol, 23, pp. 1303-1312DEGASPERI, G.R., VELHO, J.A., ZECCHIN, K.G., SOUZA, C.T., VELLOSO, L.A., BORECKÝ, J., CASTILHO, R.F., VERCESI, A.E., Role of mitochondria in the immune response to cancer: A central role for Ca 2+ (2006) J Bioenerg Biomembr, 38, pp. 1-10DEGASPERI, G.R., ZECCHIN, K.G., BORECKY, J., CRUZ-HOFLING, M.A., CASTILHO, R.F., VELLOSO, L.A., GUIMARÃES, F., VERCESI, A.E., Verapamil-sensitive Ca2+ channel regulation of Th1-type proliferation of splenic lymphocytes induced by Walker 256 tumor development in rats (2006) Eur J Pharmacol, 549, pp. 179-184DOROSHOW, J.H., Anthracycline antibiotic-stimulated superoxide, hydrogen peroxide, and hydroxyl radical production by NADH dehydrogenase (1983) Cancer Res, 43, pp. 4543-4551FESKE, S., Calcium signalling in lymphocyte activation and disease (2007) Nat Rev Immunol, 7, pp. 690-702FRIBERG, H., FERRAND-DRAKE, M., BENGTSSON, F., HALESTRAP, A.P., WIELOCH, T., Cyclosporin A, but not FK 506, protects mitochondria and neurons against hypoglycemic damage and implicates the mitochondrial permeability transition in cell death (1998) JNeurosci, 18, pp. 5151-5159GALAT, A., Peptidylprolyl cis/trans isomerases (immunophilins): Biological diversity - targets - functions (2003) Curr Top Med Chem, 3, pp. 1315-1347GIARDINI, C., LA NASA, G., CONTU, L., GALIMBERTI, M., POLCHI, P., ANGELUCCI, E., BARONCIANI, D., LUCARELLI, G., Desferrioxamine therapy induces clearance of iron deposits after bone marrow transplantation for thalassemia: Case report (1993) Bone Marrow Transplant, (SUPPL. 1), pp. 108-110GOLDSTEIN, S., CZAPSKI, G., Transition metal ions and oxygen radicals (1990) Int Rev Exp Pathol, 31, pp. 133-164GREEN, D.R., KROEMER, G., The pathophysiology of mitochondrial cell death (2004) Science, 305, pp. 626-629GREEN, D.R., REED, J.C., Mitochondria and apoptosis (1998) Science, 281, pp. 1309-1312GRIFFITHS, E.J., HALESTRAP, A.P., Further evidence that cyclosporin A protects mitochondria from calcium overload, by inhibiting a matrix peptidyl-prolyl cis-trans isomerase. Implications for the immunosuppressive and toxic effects of cyclosporin (1991) Biochem J, 274, pp. 611-614GROSSMAN, Z., MIN, B., MEIER-S, CHELLERSHEIM, M., PAUL, W.E., Concomitant regulation of T-cell activation and homeostasis (2004) Nat Rev Immunol, 4, pp. 387-395HALLIWELL, B., Protection against tissue damage in vivo by desferrioxamine: What is its mechanism of action? (1989) Free Radic Biol Med, 7, pp. 645-651HARTLEY, A., DAVIES, M., RICE- EVANS, C., Desferrioxamine as a lipid chain-breaking antioxidant in sickle erythrocyte membranes (1990) FEBS Lett, 264, pp. 145-148HERMISTON, M.L., XU, Z., MAJETI, R., WEISS, A., Reciprocal regulation of lymphocyte activation by tyrosine kinases and phosphatases (2002) J Clin Invest, 109, pp. 9-14HOE, S., ROWLEY, D.A., HALLIWELL, B., Reactions of ferrioxamine and desferrioxamine with the hydroxyl radical (1982) Chem Biol Interact, 41, pp. 75-81JOCELYN, P.C., DICKSON, J., Glutathione and the mitochondrial reduction of hydroperoxides (1980) BiochimBiophys Acta, 590, pp. 1-12KENNEDY, C.H., CHURCH, D.F., WINSTON, G.W., PRYOR, W.A., tert-Butyl hydroperoxide-induced radical production in rat liver mitochondria (1992) Free Radic Biol Med, 12, pp. 381-387KOWALTOWSKI, A.J., CASTILHO, R.F., VERCESI, A.E., Mitochondrial permeability transition and oxidative stress (2001) FEBS Lett, 495, pp. 12-15KRAMMER PH, ARNOLD R AND LAVRIK IN. 2007. Life and death in peripheral T cells. Nat Rev Immunol 7: 532-542LEMASTERS, J.J., ET AL., The mitochondrial permeability transition in cell death: A common mechanism in necrosis, apoptosis and autophagy (1998) Biochim Biophys Acta, 1366, pp. 177-196MACKALL, C.L., FLEISHER, T.A., BROWN, M.R., MAGRATH, I.T., SHAD, A.T., HOROWITZ, M.E., WEXLER, L.H., GRESS, R.E., Lymphocyte depletion during treatment with intensive chemotherapy for cancer (1994) Blood, 84, pp. 2221-2228MARTIN, S.J., REUTELINGSPERGER, C.P.M., MCGAHON, A.J., RADER, J., VAN SCHIE, R.C.A.A., LAFACE, D.M., GREEN, D.R., Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: Inhibition by overex-pression of Bcl-2 and Abl (1995) J Exp Med, 182, pp. 1-12MATHER, M.W., ROTTENBERG, H., The inhibition of calcium signaling in T lymphocytes from old mice results from enhanced activation of the mitochondrial permeability transition pore (2002) Mech Ageing Dev, 123, pp. 707-724NIEMINEN, A.L., BYRNE, A.M., HERMAN, B., LEMASTERS, J.J., Mitochondrial permeability transition in hepatocytes induced by t-BuOOH: NAD(P)H and reactive oxygen species (1997) Am J Physiol, 272, pp. C1286-C1294QUINTANA, A., GRIESEMER, D., SCHWARZ, E.C., HOTH, M., Calcium-dependent activation of T-lymphocytes (2005) Pflugers Arch, 450, pp. 1-12ROTTENBERG, H., WU, S., Quantitative assay by flow cytometry of the mitochondrial membrane potential in intact cells (1998) Biochim Biophys Acta, 1404, pp. 393-404ROY, C.R., Immunology: Professional secrets (2003) Nature, 425, pp. 351-352STAHNKE, K., FULDA, S., FRIESEN, C., STRAUSS, G., DEBATIN, K.M., Activation of apoptosis pathways in peripheral blood lymphocytes by in vivo chemotherapy (2001) Blood, 98, pp. 3066-3073WALLACE, K.B., Doxorubicin-induced cardiac mitochondrionopathy (2003) Pharmacol Toxicol, 93, pp. 105-115WILLIAMS, M.S., KWON, J., T cell receptor stimulation, reactive oxygen species, and cell signaling (2004) Free Radic Biol Med, 37, pp. 1144-1151ZORATTI, M., SZABO, I., The mitochondrial permeability transition (1995) Biochim Biophys Acta, 1241, pp. 139-17

3,5,3'-triiodothyronine Induces Mitochondrial Permeability Transition Mediated By Reactive Oxygen Species And Membrane Protein Thiol Oxidation

Ca2+-loaded rat liver mitochondria treated with 3,5,3'- triiodothyronine (T3) undergo nonspecific inner membrane permeabilization, as evidenced by mitochondrial swelling, a decrease in membrane potential (ΔΨ), and an increase in the rate of oxygen uptake. T3 analogues thyroxine (T4), 3',5'-diiodothyronine (T2), and 3,5',3'-triiodothyronine (reverse T3), in decreasing order of potency, resulted in a similar but less extensive effect. Permeabilization induced by T3 is dependent on Ca2+ (1 μM) and T3 (0.5-25 μM) concentrations and is inhibited by cyclosporin A, a known inhibitor of mitochondrial permeability transition. Catalase or dithiothreitol also prevents membrane permeabilization, suggesting the participation of membrane protein thiol group oxidation induced by reactive oxygen species. The determination of the mitochondrial membrane protein thiol group content after treatment with Ca2+ and T3 shows a significant decrease, due to thiol oxidation. When mitochondria are incubated in the presence of inorganic phosphate and the protonophore carbonyl cyanide p- trifluoromethoxyphenylhydrazone, mitochondrial swelling still occurs after treatment with T3 and high Ca2+ concentrations, suggesting that mitochondrial permeabilization is not dependent on T3-induced ΔΨ or matrix pH alterations. Under these experimental conditions, when no oxygen is present in the incubation medium, no permeabilization occurs, suggesting that the permeabilization is dependent on mitochondrial-generated reactive oxygen species. Confirming this hypothesis, superoxide generation in a suspension of submitochondrial particles is increased when T3 is present. Our results lead to the conclusion that T3 induces a situation of oxidative stress in isolated liver mitochondria, with Ca2+-mediated membrane protein thiol oxidation and nonspecific inner membrane permeabilization.3541151157Soboll, S., (1993) Biochim. Biophys. Acta, 1144, pp. 1-16Luciakova, K., Nelson, D., (1992) Eur. J. Biochem., 207, pp. 247-251Joste, V., Goitom, Z., Nelson, B.D., (1989) Eur. J. Biochem., 180, pp. 235-240Van Itallie Ch., M., (1990) Endocrinology, 127, pp. 55-62Hulbert, A.J., Augee, M.L., Raison, J.K., (1976) Biochim. Biophys. Acta, 455, pp. 597-601Hoch, F.L., (1988) Prog. Lipid Res., 27, pp. 199-270Sterling, K., (1986) Endocrinology, 119, pp. 292-295Mak, I.T., Shrago, E., Elson, C.E., (1983) Arch. Biochem. Biophys., 226, pp. 317-323Verhoeven, A.J., Kamer, P., Groen, A.K., Tager, J.M., (1985) Biochem. J., 226, pp. 183-192Greif, R.L., Fiskum, G., Sloane, D.A., Lehninger, A.L., (1982) Biochem. Biophys. Res. Commun., 108, pp. 307-314Harris, E.J., Al-Shaikhaly, M., Baum, H., (1979) Biochem. J., 182, pp. 455-464Brand, M.D., Steverding, D., Kadenbach, B., Stevenson, P.M., Hafner, R.P., (1992) Eur. J. Biochem., 206, pp. 775-781Kalderon, B., Hermesh, O., Bar-Tana, J., (1995) Endocrinology, 136, pp. 3552-3556Zoratti, M., Szabò, I., (1995) Biochim. Biophys. Acta, 1241, pp. 139-176Kowaltowski, A.J., Castilho, R.F., Grijalba, M.T., Bechara, E.J.H., Vercesi, A.E., (1996) J. Biol. Chem., 271, pp. 2929-2934Castilho, R.F., Kowaltowski, A.J., Meinicke, A.R., Bechara, E.J.H., Vercesi, A.E., (1995) Free Radical Biol. Med., 18, pp. 479-486Kowaltowski, A.J., Castilho, R.F., Vercesi, A.E., (1995) Am. J. Physiol., 269, pp. 141-C147Fagian, M.M., Pereira-Da-Silva, L., Martins, I.S., Vercesi, A.E., (1990) J. Biol. Chem., 265, pp. 19955-19960Castilho, R.F., Kowaltowski, A.J., Vercesi, A.E., (1996) J. Bioenerg. Biomembr., 28, pp. 523-529Bindoli, A., Callegaro, M.T., Barzon, E., Benetti, M., Rigobello, M.P., (1997) Arch. Biochem. Biophys., 342, pp. 22-28Connern, C.P., Halestrap, A.P., (1994) Biochem. J., 302, pp. 321-324Pastorino, J.G., Snyder, J.W., Serroni, A., Hoek, J.B., Farber, J.L., (1993) J. Biol. Chem., 268, pp. 13791-13798Zamzami, N., Hirsch, T., Dallaporta, B., Petit, P.X., Kroemer, G., (1997) J. Bioenerg. Biomembr., 29, pp. 185-193Lemasters, J.J., Nieminen, A.-L., (1997) Biosci. Rep., 17, pp. 281-291Gregg, C.T., (1966) Methods Enzymol., 10, pp. 181-185Åkerman, K.E.O., Wikström, K.F., (1976) FEBS Lett., 68, pp. 191-197Kowaltowski, A.J., Vercesi, A.E., Castilho, R.F., (1997) Biochim. Biophys Acta, 1318, pp. 395-402Boveris, A., (1985) Methods Enzymol., 105, pp. 429-435Skulachev, V.P., (1996) Q. Rev. Biophys., 29, pp. 169-202Bernardi, P., Broekemeier, K.M., Pfeiffer, D.R., (1994) J. Bioenerg. Biomembr., 26, pp. 509-517Petronilli, V., Constantini, P., Scorrano, L., Colonna, R., Passamonti, S., Bernardi, P., (1994) J. Biol. Chem., 269, pp. 16638-16642Malkevitch, N.V., Dedukhova, R.A., Simonian, R.A., Skulachev, V.P., Starkov, A.A., (1997) FEBS Lett., 412, pp. 173-178Rydström, J., (1977) Biochim. Biophys. Acta, 463, pp. 155-184Hoek, J.B., Rydström, J., (1988) Biochem. J., 254, pp. 1-10Vercesi, A.E., Kowaltowski, A.J., Grijalba, M.T., Meinicke, A.R., Castilho, R.F., (1997) Biosc. Rep., 17, pp. 43-52Turrens, J.F., Beconi, M., Barilla, J., Chavez, U.B., McCord, J.M., (1991) Free Radicals Res. Commun., 1213, pp. 681-689Larsen, P.R., The thyroid (1992) Cecil - Textbook of Medicine, , Philadelphia: Saunders. p. 1248-1271Fernandez, V., Llesuy, S., Solari, L., Kipreos, K., Videla, L.A., Boveris, A., (1988) Free Radicals Res. Commun., 5, pp. 77-84Fernandez, V., Videla, L.A., (1996) Toxicol. Lett., 84, pp. 149-153Asayama, K., Dobashi, K., Hayashibe, H., Megata, Y., Kato, K., (1987) Endocrinology, 121, pp. 2112-2118Martensson, J., Goodwin, C.W., Blake, R., (1992) Metabolism, 41, pp. 273-27

Glutamate Excitotoxicity And Neuronal Energy Metabolism

The bioenergetic properties of the in situ mitochondria play a central role in controlling the susceptibility of neurons to acute or chronic neurodegenerative stress. The mitochondrial membrane potential, Δψ(m), is the parameter that controls three interrelated mitochondrial functions of great relevance to neuronal survival: namely, ATP synthesis, Ca2+ accumulation, and superoxide generation. The in vitro model we study is the rat cerebellar granule cell in primary culture and its susceptibility to NMDA receptor-mediated necrosis, which is preceded by a delayed failure of cytoplasmic Ca2+ homeostasis ('delayed Ca2+ deregulation,' DCD). DCD is not caused by a failure of mitochondrial ATP synthesis since it also occurs in cells maintained purely by glycolysis. The in situ mitochondria maintain a Δψ(m), sufficient for ATP synthesis throughout the exposure of the cells to glutamate until DCD occurs. Even at that stage it appears that mitochondrial depolarization may be an effect of DCD rather than a primary cause. This somewhat unorthodox view resolves a number of apparent paradoxes, such as observations of enhanced superoxide generation by in situ mitochondria during excitotoxic exposure, since isolated mitochondria generate superoxide only under conditions of high Δψ(m). Mitochondrial depolarization by selective inhibitors that do not deplete cellular ATP is acutely neuroprotective.893112Tymianski, M., Charlton, M.P., Carlen, P.L., Tator, C.H., Source specificity of early calcium neurotoxicity in cultured embryonic spinal neurons (1993) J. Neurosci., 13, pp. 2085-2104Sattler, R., Charlton, M.P., Hafner, M., Tymianski, M., Distinct influx pathways, not calcium load, determine neuronal vulnerability to calcium neurotoxicity (1998) J. Neurochem., 71, pp. 2349-2364Peng, T.I., Greenamyre, J.T., Privileged access to mitochondria of calcium influx through N-methyl-D-aspartate receptors (1998) Mol. Pharmacol., 53, pp. 974-980Hartley, D.M., Kurth, M.C., Bjerkness, L., Weiss, J.H., Choi, D.W., Glutamate receptor-induced 45Ca2+ accumuation in cortical cell culture correlated with subsequent neuronal degeneration (1993) J. Neurosci., 13, pp. 1993-2000Eimerl, S., Schramm, M., The quantity of calcium that appears to induce neuronal death (1994) J. Neurochem., 62, pp. 1223-1226Kiedrowski, L., Wroblewski, J.T., Costa, E., Intracellular sodium concentration in cultured cerebellar granule cells challenged with glutamate (1994) Mol. Pharmacol., 45, pp. 1050-1054Beal, M.F., Howell, N., Bodis-Wollner, I., (1997) Mitochondria and Free Radicals in Neurodegenerative Disease, , Wiley-Lis. New YorkBudd, S.L., Nicholls, D.G., Mitochondrial calcium regulation and acute glutamate excitotoxicity in cultured cerebellar granule cells (1996) J. Neurochem., 67, pp. 2282-2291Castilho, R.F., Hansson, O., Ward, M.W., Budd, S.L., Nicholls, D.G., Mitochondrial control of acute glutamate excitotoxicity in cultured cerebellar granule cells (1998) J. Neurosci., 18, pp. 10277-10286Nicholls, D.G., Budd, S.L., Ward, M.W., Castilho, R.F., Excitotoxicity and mitochondria (1999) Mitochondria in the Life and Death of the Cell, , G.C. Brown, D.G. Nicholls & C. Cooper, Eds. Portland Press. London. In pressNicholls, D.G., The regulation of extra-mitochondrial free Ca by rat liver mitochondria (1978) Biochem. J., 176, pp. 463-474Werth, J.L., Thayer, S.A., Mitochondria buffer physiological calcium loads in cultured rat dorsal root ganglion neurons (1994) J. Neurosci., 14, pp. 346-356White, R.J., Reynolds, I.J., Mitochondria and Na+/Ca2+ exchange buffer glutamate-induced calcium loads in cultured cortical neurons (1995) J. Neurosci., 15, pp. 1318-1328Kiedrowski, L., Costa, E., Glutamate-induced destabilization of intracellular calcium concentration homeostasis in cultured cerebellar granule cells: Role of mitochondria in calcium buffering (1995) Mol. Pharmacol., 47, pp. 140-147Wang, G.J., Thayer, S.A., Sequestration of glutamate-induced Ca2+ loads by mitochondria in cultured rat hippocampal neurons (1996) J. Neurophysiol., 76, pp. 1611-1621Schinder, A.F., Olson, E.C., Spitzer, N.C., Montal, M., Mitochondrial dysfunction is a primary event in glutamate excitotoxicity (1996) J. Neurosci., 16, pp. 6125-6133Khodorov, B.I., Pinelis, V.G., Storozhevykh, T., Vergun, O.V., Vinskaya, N.P., Dominant role of mitochondria in protection against a delayed neuronal Ca overload induced by endogenous excitatory amino acids following a glutamate pulse (1996) FEBS Lett., 393, pp. 135-138Isaev, N.K., Zorov, D.B., Stelmashook, E.V., Uzbekov, R.E., Kozhemyakin, M.B., Victorov, I.V., Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca2+-dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria (1996) FEBS Lett., 392, pp. 143-147White, R.J., Reynolds, I.J., Mitochondria accumulate Ca2+ following intense glutamate stimulation of cultured rat forebrain neurones (1997) J. Physiol. (Lond.), 498, pp. 31-47Bernardi, P., Basso, E., Colonna, R., Costantini, P., Di Lisa, F., Eriksson, O., Fontaine, E., Scorrano, L., Perspectives on the mitochondrial permeability transition (1998) Biochim. Biophys. Acta Bio-energetics, 1365, pp. 200-206Reynolds, I.J., Hastings, T.G., Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation (1995) J. Neurosci., 15, pp. 3318-3327Dugan, L.L., Sensi, S.L., Canzoniero, L.M.T., Handran, S.D., Rothman, S.M., Lin, T.S., Goldberg, M.P., Choi, D.W., Mitochondrial production of reactive oxygen species in cortical neurons following exposure to NMDA (1995) J. Neurosci., 15, pp. 6377-6388Bindokas, V.P., Jordan, J., Lee, C.C., Miller, R.J., Superoxide production in rat hippocampal neurons: Selective imaging with hydroethidine (1996) J. Neurosci., 16, pp. 1324-1336Budd, S.L., Nicholls, D.G., A re-evaluation of the role of mitochondria in neuronal calcium homeostasis (1996) J. Neurochem., 66, pp. 403-411Kiedrowski, L., Brooker, G., Costa, E., Wroblewski, J.T., Glutamate impairs neuronal calcium extrusion while reducing sodium gradient (1994) Neuron, 12, pp. 295-300Pinelis, V.G., Segal, M., Greenberger, V., Khodorov, B.I., Changes in cytosolic sodium caused by a toxic glutamate treatment of cultured hippocampal neurons (1994) Biochem. Mol. Biol. Int., 32, pp. 475-482Khodorov, B.I., Fayuk, D.A., Koshelev, S.G., Vergun, O.V., Pinelis, V.G., Vinskaya, N.P., Storozhevykh, T.P., Dubinsky, J.M., Effect of a prolonged glutamate challenge on plasmalemmal calcium permeability in mammalian central neurones. Mn2+ as a tool to study calcium influx pathways (1996) Int. J. Neurosci., 88, pp. 215-241Ankarcrona, M., Dypbukt, J.M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S.A., Nicotera, P., Glutamate-induced neuronal death: A succession of necrosis or apoptosis depending on mitochondrial function (1995) Neuron, 15, pp. 961-973White, R.J., Reynolds, I.J., Mitochondrial depolarization in glutamate-stimulated neurons: An early signal specific to excitotoxin exposure (1996) J. Neurosci., 16, pp. 5688-5697Khodorov, B.I., Pinelis, V., Vergun, O., Storozhevykh, T., Vinskaya, N., Mitochondrial deenergization underlies neuronal calcium overload following a prolonged glutamate challenge (1996) FEBS Lett., 397, pp. 230-234Ankarcrona, M., Dypbukt, J.M., Orrenius, S., Nicotera, P., Calcineurin and mitochondrial function in glutamate-induced neuronal cell death (1996) FEBS Lett., 394, pp. 321-324Prehn, J.H.M., Mitochondrial transmembrane potential and free radical production in excitotxic neurodegeneration (1998) Naunyn-Schmiedebergs Arch. Pharmacol., 357, pp. 316-322Kiedrowski, L., The difference between mechanisms of kainate and glutamate excitotoxicity in vitro: Osmotic lesion versus mitochondrial depolarization (1998) Restor. Neurol. Neurosci., 12, pp. 71-79Keelan, J., Vergun, O., Khodorov, B.I., Duchen, M.R., Calcium-dependent mitochondrial depolarization specific to toxic glutamate depolarization in cultured rat hippocampal neurones (1998) J. Physiol. (Lond), 506, pp. 75PEhrenberg, B., Montana, V., Wei, M.D., Wuskell, J.P., Loew, L.M., Membrane potential can be determined in individual cells from the nernstian distribution of cationic dyes (1988) Biophys. J., 53, pp. 785-794Boveris, A., Oshino, N., Chance, B., The cellular production of hydrogen peroxide (1972) Biochem. J., 128, pp. 617-630Negre-Salvayre, A., Hirtz, C., Carrera, G., Cazenave, R., Troly, M., Salvayre, R., Pénicaud, L., Casteilla, L., Role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation (1997) FASEB J., 11, pp. 809-815Zhang, L., Yu, L.D., Yu, C.A., Generation of superoxide anion by succinate-cytochrome c reductase from bovine heart mitochondria (1998) J. Biol. Chem., 273, pp. 33972-33976Budd, S.L., Castilho, R.F., Nicholls, D.G., Mitochondrial membrane potential and hydroethidine-monitored superoxide generation in cerebellar granule cells (1997) FEBS Lett., 415, pp. 21-2

Sickle-cell anemia and latent diastolic dysfunction: echocardiographic alterations

Sickle-cell anemia (SCA) is a disease that can cause systemic complications, such as multiple organ dysfunction due to vaso-occlusion and endothelial activation. The genetic cause of the disease is a substitution of the amino acid glutamic acid for valine1044e3033sem informaçãosem informaçã

Mitochondrial Energy Metabolism And Redox State In Dyslipidemias

Changes in mitochondrial function are intimately associated with metabolic diseases. Here, we review recent evidence relating alterations in mitochondrial energy metabolism, ion transport and redox state in hypercholesterolemia and hypertriglyceridemia. We focus mainly on changes in mitochondrial respiration, K+ and Ca2+ transport, reactive oxygen species generation and susceptibility to mitochondrial permeability transition. © 2007 IUBMB.5904/05/15263268Newmeyer, D.D., Ferguson-Miller, S., Mitochondria: Releasing power for life and unleashing the machineries of death (2003) Cell, 112, pp. 481-490Green, D.R., Kroemer, G., The pathophysiology of mitochondrial cell death (2004) Science, 305, pp. 626-629Orrenius, S., Gogvadze, V., Zhivotovsky, B., Mitochondrial oxidative stress: Implications for cell death (2006) Annu. Rev. Pharmacol. Toxicol, 47, pp. 143-183Vercesi, A.E., Kowaltowski, A.J., Oliveira, H.C., Castilho, R.F., Mitochondrial Ca2+ transport, permeability transition and oxidative stress in cell death: Implications in cardiotoxicity, neurodegeneration and dyslipidemias (2006) Front. Biosci, 11, pp. 2554-2564Turrens, J.F., Mitochondrial formation of reactive oxygen species (2003) J. Physiol, 552, pp. 335-344Korshunov, S.S., Skulachev, V.P., Starkov, A.A., High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria (1997) FEBS Lett, 416, pp. 15-18Grijalba, M.T., Vercesi, A.E., Schreier, S., Ca 2+-induced increased lipid packing and domain formation in submitochondrial particles. A possible early step in the mechanism of Ca 2+-stimulated generation of reactive oxygen species by the respiratory chain (1999) Biochemistry, 38, pp. 13279-13287Kowaltowski, A.J., Castilho, R.F., Vercesi, A.E., Mitochondrial permeability transition and oxidative stress (2001) FEBS Lett, 495, pp. 12-15Fagian, M.M., Pereira-da-Silva, L., Martins, I.S., Vercesi, A.E., Membrane protein thiol cross-linking associated with the permeabilization of the inner mitochondrial membrane by Ca2+ plus prooxidants (1990) J. Biol. Chem, 265, pp. 19955-19960Crompton, M., The mitochondrial permeability transition pore and its role in cell death (1999) Biochem. J, 341, pp. 233-249Zoratti, M., Szabo, I., The mitochondrial permeability transition (1995) Biochim. Biophys. Acta, 1241, pp. 139-176Lehninger, A.L., Vercesi, A., Bababunmi, E.A., Regulation of Ca2+ release from mitochondria by the oxidationreduction state of pyridine nucleotides (1978) Proc. Natl. Acad. Sci. USA, 75, pp. 1690-1694Kim, J.S., He, L., Lemasters, J.J., Mitochondrial permeability transition: A common pathway to necrosis and apoptosis (2003) Biochem. Biophys. Res. Commun, 304, pp. 463-470Brown, M.S., Goldstein, J.L., A receptor-mediated pathway for cholesterol homeostasis (1986) Science, 232, pp. 34-47Stokes III, J., Kannel, W.B., Wolf, P.A., Cupples, L.A., D'Agostino, R.B., The relative importance of selected risk factors for various manifestations of cardiovascular disease among men and women from 35 to 64 years old: 30 years of follow-up in the Framingham Study (1987) Circulation, 75, pp. V65-V73Chisolm, G.M., Steinberg, D., The oxidative modification hypothesis of atherogenesis: An overview (2000) Free Radic. Biol. Med, 28, pp. 1815-1826Witztum, J.L., Steinberg, D., Role of oxidized low density lipoprotein in atherogenesis (1991) J. Clin. Invest, 88, pp. 1785-1792Morel, D.W., DiCorleto, P.E., Chisolm, G.M., Endothelial and smooth muscle cells alter low density lipoprotein in vitro by free radical oxidation (1984) Arteriosclerosis, 4, pp. 357-364Lamb, D.J., Wilkins, G.M., Leake, D.S., The oxidative modification of low density lipoprotein by human lymphocytes (1992) Atherosclerosis, 92, pp. 187-192Oliveira, H.C., Cosso, R.G., Alberici, L.C., Maciel, E.N., Salerno, A.G., Dorighello, G.G., Velho, J.A., Vercesi, A.E., Oxidative stress in atherosclerosis-prone mouse is due to low antioxidant capacity of mitochondria (2005) FASEB J, 19, pp. 278-280Gaylor, J.L., Membrane-bound enzymes of cholesterol synthesis from lanosterol (2002) Biochem. Biophys. Res. Commun, 292, pp. 1139-1146Zmijewski, J.W., Moellering, D.R., Le Goffe, C., Landar, A., Ramachandran, A., Darley-Usmar, V.M., Oxidized LDL induces mitochondrially associated reactive oxygen/nitrogen species formation in endothelial cells (2005) Am. J. Physiol. Heart Circ. Physiol, 289, pp. H852-H861Vindis, C., Elbaz, M., Escargueil-Blanc, I., Auge, N., Heniquez, A., Thiers, J.C., Negre-Salvayre, A., Salvayre, R., Two distinct calcium-dependent mitochondrial pathways are involved in oxidized LDL-induced apoptosis (2005) Arterioscler. Thromb. Vasc. Biol, 25, pp. 639-645Jo, S.H., Son, M.K., Koh, H.J., Lee, S.M., Song, I.H., Kim, Y.O., Lee, Y.S., Huh, T.L., Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase (2001) J. Biol. Chem, 276, pp. 16168-16176Koh, H.J., Lee, S.M., Son, B.G., Lee, S.H., Ryoo, Z.Y., Chang, K.T., Park, J.W., Huh, T.L., Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid metabolism (2004) J. Biol. Chem, 279, pp. 39968-39974Hoek, J.B., Rydstrom, J., Physiological roles of nicotinamide nucleotide transhydrogenase (1988) Biochem. J, 254, pp. 1-10Velho, J.A., Okanobo, H., Degasperi, G.R., Matsumoto, M.Y., Alberici, L.C., Cosso, R.G., Oliveira, H.C., Vercesi, A.E., Statins induce calcium-dependent mitochondrial permeability transition (2006) Toxicology, 219, pp. 124-132Kaneta, S., Satoh, K., Kano, S., Kanda, M., Ichihara, K., All hydrophobic HMG-CoA reductase inhibitors induce apoptotic death in rat pulmonary vein endothelial cells (2003) Atherosclerosis, 170, pp. 237-243Kubota, T., Fujisaki, K., Itoh, Y., Yano, T., Sendo, T., Oishi, R., Apoptotic injury in cultured human hepatocytes induced by HMG-CoA reductase inhibitors (2004) Biochem. Pharmacol, 67, pp. 2175-2186Clark, L.T., Treating dyslipidemia with statins: The risk-benefit profile (2003) Am. Heart J, 145, pp. 387-396Assmann, G., Brewer Jr., H.B., Genetic (primary) forms of hypertriglyceridemia (1991) Am. J. Cardiol, 68, pp. 13A-16AMancini, M., Steiner, G., Betteridge, D.J., Pometta, D., Acquired (secondary) forms of hypertriglyceridemia (1991) Am. J. Cardiol, 68, pp. 17A-21AMalloy, M.J., Kane, J.P., A risk factor for atherosclerosis: Triglyceride-rich lipoproteins (2001) Adv. Intern. Med, 47, pp. 111-136Walsh, A., Azrolan, N., Wang, K., Marcigliano, A., O'Connell, A., Breslow, J.L., Intestinal expression of the human apoA-I gene in transgenic mice is controlled by a DNA region 3′ to the gene in the promoter of the adjacent convergently transcribed apoC-III gene (1993) J. Lipid Res, 34, pp. 617-623Aalto-Setala, K., Weinstock, P.H., Bisgaier, C.L., Wu, L., Smith, J.D., Breslow, J.L., Further characterization of the metabolic properties of triglyceride-rich lipoproteins from human and mouse apoC-III transgenic mice (1996) J. Lipid. Res, 37, pp. 1802-1811Amaral, M.E., Oliveira, H.C., Carneiro, E.M., Delghingaro-Augusto, V., Vieira, E.C., Berti, J.A., Boschero, A.C., Plasma glucose regulation and insulin secretion in hypertriglyceridemic mice (2002) Horm. Metab. Res, 34, pp. 21-26Alberici, L.C., Oliveira, H.C., Bighetti, E.J., de Faria, E.C., Degaspari, G.R., Souza, C.T., Vercesi, A.E., Hypertriglyceridemia increases mitochondrial resting respiration and susceptibility to permeability transition (2003) J. Bioenerg. Biomembr, 35, pp. 451-457Catisti, R., Vercesi, A.E., The participation of pyridine nucleotides redox state and reactive oxygen in the fatty acid-induced permeability transition in rat liver mitochondria (1999) FEBS Lett, 464, pp. 97-101Brand, M.D., Esteves, T.C., Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3 (2005) Cell Metab, 2, pp. 85-93Bao, S., Kennedy, A., Wojciechowski, B., Wallace, P., Ganaway, E., Garvey, W.T., Expression of mRNAs encoding uncoupling proteins in human skeletal muscle: Effects of obesity and diabetes (1998) Diabetes, 47, pp. 1935-1940Hidaka, S., Yoshimatsu, H., Kakuma, T., Sakino, H., Kondou, S., Hanada, R., Oka, K., Sakata, T., Tissue-specific expression of the uncoupling protein family in streptozotocin-induced diabetic rats (2000) Proc. Soc. Exp. Biol. Med, 224, pp. 172-177Gong, D.W., He, Y., Karas, M., Reitman, M., Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin (1997) J. Biol. Chem, 272, pp. 24129-24132Samec, S., Seydoux, J., Dulloo, A.G., Post-starvation gene expression of skeletal muscle uncoupling protein 2 and uncoupling protein 3 in response to dietary fat levels and fatty acid composition: A link with insulin resistance (1999) Diabetes, 48, pp. 436-441Nisoli, E., Carruba, M.O., Tonello, C., Macor, C., Federspil, G., Vettor, R., Induction of fatty acid translocase/CD36, peroxisome proliferator-activated receptor-gamma2, leptin, uncoupling proteins 2 and 3, and tumor necrosis factor-alpha gene expression in human subcutaneous fat by lipid infusion (2000) Diabetes, 49, pp. 319-324Garlid, K.D., Paucek, P., Mitochondrial potassium transport: The K+ cycle (2003) Biochim. Biophys. Acta, 1606, pp. 23-41Facundo, H.T., Fornazari, M., Kowaltowski, A.J., Tissue protection mediated by mitochondrial K+ channels (2006) Biochim. Biophys. Acta, 1762, pp. 202-212Alberici, L.C., Oliveira, H.C., Patricio, P.R., Kowaltowski, A.J., Vercesi, A.E., Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP-sensitive K+ channel activity (2006) Gastroenterology, 131, pp. 1228-1234Rothwell, N.J., Stock, M.J., Energy expenditure of 'cafeteria'-fed rats determined from measurements of energy balance and indirect calorimetry (1982) J. Physiol, 328, pp. 371-377Rothwell, N.J., Stock, M.J., A role for brown adipose tissue in diet-induced thermogenesis (1979) Nature, 281, pp. 31-35St-Pierre, J., Buckingham, J.A., Roebuck, S.J., Brand, M.D., Topology of superoxide production from different sites in the mitochondrial electron transport chain (2002) J. Biol. Chem, 277, pp. 44784-44790Zhang, D.X., Chen, Y.F., Campbell, W.B., Zou, A.P., Gross, G.J., Li, P.L., Characteristics and superoxide-induced activation of reconstituted myocardial mitochondrial ATP-sensitive potassium channels (2001) Circ. Res, 89, pp. 1177-1183Facundo, H. T. F., de Paula, J. G., and Kowaltowski, A. J. (2007). Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production. Free Radic. Biol. Med. doi 10.1016/jfreeradbiomed.2007.01.001Ferranti, R., da Silva, M.M., Kowaltowski, A.J., Mitochondrial ATP-sensitive K+ channel opening decreases reactive oxygen species generation (2003) FEBS Lett, 536, pp. 51-5