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Gradual Alteration of Mitochondrial Structure and Function by β-Amyloids: Importance of Membrane Viscosity Changes, Energy Deprivation, Reactive Oxygen Species Production, and Cytochrome c Release

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Abstract

Intracellular amyloid beta-peptide (Aβ) accumulation is considered to be a key pathogenic factor in sporadic Alzheimer’s disease (AD), but the mechanisms by which it triggers neuronal dysfunction remain unclear. We hypothesized that gradual mitochondrial dysfunction could play a central role in both initiation and progression of sporadic AD. Thus, we analyzed changes in mitochondrial structure and function following direct exposure to increasing concentrations of Aβ1−42 and Aβ25−35 in order to look more closely at the relationships between mitochondrial membrane viscosity, ATP synthesis, ROS production, and cytochrome c release. Our results show the accumulation of monomeric Aβ within rat brain and muscle mitochondria. Subsequently, we observed four different and additive modes of action of Aβ, which were concentration dependent: (i) an increase in mitochondrial membrane viscosity with a concomitant decrease in ATP/O, (ii) respiratory chain complexes inhibition, (iii) a potentialization of ROS production, and (iv) cytochrome c release.

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References

  • Anandatheerthavarada, H. K., Biswas, G., Robin, M. A., and Avadhani, N. G. (2003). J. Cell Biol. 161(1), 41–54.

    Article  PubMed  Google Scholar 

  • Bales, K. R., Verina, T., Dodel, R. C., Du, Y., Altstiel, L., Bender, M., Hyslop, P., Johnstone, E. M., Little, S. P., Cummins, D. J., Piccardo, P., Ghetti, B., and Paul, S. M. (1997). Nat. Genet. 17, 263–264.

    PubMed  Google Scholar 

  • Behl, C., Davis, J. B., Lesley, R. and Schubert, D. (1994). Cell 77, 817–827.

    Article  PubMed  Google Scholar 

  • Ben-Shachar, D., and Laifenfeld, D. (2004). Int. Rev. Neurobiol. 59, 273–296.

    Article  PubMed  Google Scholar 

  • Bigl, M., and Eschrich, K. (1995). Neurochem. Int. 26, 69–75.

    Article  PubMed  Google Scholar 

  • Blass, J. P. (2003). Neurol. Res. 25, 556–566.

    Article  PubMed  Google Scholar 

  • Bosetti, F., Brizzi, F., Barogi, S., Mancuso, M., Siciliano, G., Tendi, E. A., Murri, L., Rapoport, S. I., and Solaini, G. (2002). Neurobiol. Aging 23, 371–376.

    Article  PubMed  Google Scholar 

  • Burdick, D., Kosmoski, J., Knauer, M. F., and Glabe, C. G. (1997). Brain Res. 746, 275–284.

    Article  PubMed  Google Scholar 

  • Canevari, L., Abramov, A. Y., and Duchen, M. R. (2004). Neurochem. Res. 29, 637–650.

    Article  PubMed  Google Scholar 

  • Canevari, L., Clark, J. B., and Bates, T. E. (1999). FEBS Lett. 457, 131–134.

    Article  PubMed  Google Scholar 

  • Cardoso, S. M., Proenca, M. T., Santos, S., Santana, I., and Oliveira, C. R. (2004). Neurobiol. Aging 25, 105–110.

    Article  PubMed  Google Scholar 

  • Casley, C. S., Canevari, L., Land, J. M., Clark, J. B., and Sharpe, M. A. (2002a). J. Neurochem. 80, 91–100.

    Article  Google Scholar 

  • Casley, C. S., Land, J. M., Sharpe, M. A., Clark, J. B., Duchen, M. R., and Canevari, L. (2002b). Neurobiol. Dis. 10, 258–267.

    Article  Google Scholar 

  • Chagnon, P., Betard, C., Robitaille, Y., Cholette, A., and Gauvreau, D. (1995). Neuroreport 6, 711–715.

    PubMed  Google Scholar 

  • Chandrasekaran, K., Hatanpaa, K., Brady, D. R., and Rapoport, S. I. (1996). Exp. Neurol. 142, 80–88.

    Article  PubMed  Google Scholar 

  • Chui, D. H., Dobo, E., Makifuchi, T., Akiyama, H., Kawakatsu, S., Petit, A., Checler, F., Araki, W., Takahashi, K., and Tabira, T. (2001). J. Alzheimers Dis. 3, 231–239.

    PubMed  Google Scholar 

  • Cotman, C. W., Pike, C. J., and Copani, A. (1992). Neurobiol. Aging 13, 587–590.

    Article  PubMed  Google Scholar 

  • D’Andrea, M. R., Nagele, R. G., Wang, H. Y., Peterson, P. A., and Lee, D. H. (2001). Histopathology 38, 120–134.

    Article  PubMed  Google Scholar 

  • Darin, N., Moslemi, A. R., Lebon, S., Rustin, P., Holme, E., Oldfors, A., and Tulinius, M. (2003). Neuropediatrics 34, 311–317.

    Article  PubMed  Google Scholar 

  • Dawson, T. L., Gores, G. J., Nieminen, A. L., Herman, B., and Lemasters, J. J. (1993). Am. J. Physiol. 264, C961–C967.

    PubMed  Google Scholar 

  • de la Torre, J. C. (2004). Lancet Neurol. 3, 184–190.

    Article  PubMed  Google Scholar 

  • Eckert, G. P., Cairns, N. J., Maras, A., Gattaz, W. F., and Muller, W. E. (2000). Dement. Geriatr. Cogn. Disord. 11, 181–186.

    Article  PubMed  Google Scholar 

  • Fernandez-Vizarra, P., Fernandez, A. P., Castro-Blanco, S., Serrano, J., Bentura, M. L., Martinez-Murillo, R., Martinez, A., and Rodrigo, J. (2004). Histol. Histopathol. 19, 823–844.

    PubMed  Google Scholar 

  • Fukuchi, K., Pham, D., Hart, M., Li, L., and Lindsey, J. R. (1998). Am. J. Pathol. 153, 1687–1693.

    PubMed  Google Scholar 

  • Gibson, G. E., Zhang, H., Sheu, K. F., Bogdanovich, N., Lindsay, J. G., Lannfelt, L., Vestling, M., and Cowburn, R. F. (1998). Ann. Neurol. 44, 676–681.

    Article  PubMed  Google Scholar 

  • Gouras, G. K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J. P., Haroutunian, V., Buxbaum, J. D., Xu, H., Greengard, P., and Relkin, N. R. (2000). Am. J. Pathol. 156, 15–20.

    PubMed  Google Scholar 

  • Hansson, C. A., Frykman, S., Farmery, M. R., Tjernberg, L. O., Nilsberth, C., Pursglove, S. E., Ito, A., Winblad, B., Cowburn, R. F., Thyberg, J., and Ankarcrona, M. (2004). J. Biol. Chem. 279, 51654–51660.

    Article  PubMed  Google Scholar 

  • Hardy, J. A., and Higgins, G. A. (1992). Science 256, 184–185.

    PubMed  Google Scholar 

  • Hensley, K., Carney, J. M., Mattson, M. P., Aksenova, M., Harris, M., Wu, J. F., Floyd, R. A., and Butterfield, D. A. (1994). Proc. Natl. Acad. Sci. U.S.A. 91, 3270–3274.

    PubMed  Google Scholar 

  • Hirai, K., Aliev, G., Nunomura, A., Fujioka, H., Russell, R. L., Atwood, C. S., Johnson, A. B., Kress, Y., Vinters, H. V., Tabaton, M., Shimohama, S., Cash, A. D., Siedlak, S. L., Harris, P. L., Jones, P. K., Petersen, R. B., Perry, G., and Smith, M. A. (2001). J. Neurosci. 21, 3017–3023.

    PubMed  Google Scholar 

  • Holcomb, L., Gordon, M. N., McGowan, E., Yu, X., Benkovic, S., Jantzen, P., Wright, K., Saad, I., Mueller, R., Morgan, D., Sanders, S., Zehr, C., O’Campo, K., Hardy, J., Prada, C. M., Eckman, C., Younkin, S., Hsiao, K., and Duff, K. (1998). Nat. Med. 4, 97–100.

    Google Scholar 

  • Hyslop, P. A., and Sklar, L. A. (1984). Anal. Biochem. 141, 280–286.

    Article  PubMed  Google Scholar 

  • Kato, T., and Kato, N. (2000). Bipolar Disord. 2, 180–190.

    Article  PubMed  Google Scholar 

  • Kim, H. S., Lee, J. H., Lee, J. P., Kim, E. M., Chang, K. A., Park, C. H., Jeong, S. J., Wittendorp, M. C., Seo, J. H., Choi, S. H., and Suh, Y. H. (2002). Neuroreport 13, 1989–1993.

    Article  PubMed  Google Scholar 

  • Klein, W. L. (2002). Neurochem. Int. 41, 345–352.

    Article  PubMed  Google Scholar 

  • Klunk, W. E., Pettegrew, J. W., and Abraham, D. J. (1989). J. Histochem. Cytochem. 37, 1273–1281.

    PubMed  Google Scholar 

  • Knauer, M. F., Soreghan, B., Burdick, D., Kosmoski, J., and Glabe, C. G. (1992). Proc. Natl. Acad. Sci. U.S.A. 89, 7437–7441.

    PubMed  Google Scholar 

  • Lakowicz, J. (1983). Principles of Fluorescence Spectroscopy, In press, P. (ed). Plenum, New York, pp. 128–174.

  • Leissring, M. A., Farris, W., Wu, X., Christodoulou, D. C., Haigis, M. C., Guarente, L., and Selkoe, D. J. (2004). Biochem. J. Nov 1, 383 Part 3, 439–446.

  • Letellier, T., Durrieu, G., Malgat, M., Rossignol, R., Antoch, J., Deshouillers, J. M., Coquet, M., Lacombe, D., Netter, J. C., Pedespan, J. M., Redonnet-Vernhet, I., and Mazat, J. P. (2000). Lab. Invest. 80, 1019–1030.

    PubMed  Google Scholar 

  • Lewis, H. D., Beher, D., Smith, D., Hewson, L., Cookson, N., Reynolds, D. S., Dawson, G. R., Jiang, M., Van Der Ploeg, L. H., Qian, S., Rosahl, T. W., Kalaria, R. N., and Shearman, M. S. (2004). Neurobiol. Aging 25, 1175–1185.

    Article  PubMed  Google Scholar 

  • Li, Q. X., Maynard, C., Cappai, R., McLean, C. A., Cherny, R. A., Lynch, T., Culvenor, J. G., Trevaskis, J., Tanner, J. E., Bailey, K. A., Czech, C., Bush, A. I., Beyreuther, K., and Masters, C. L. (1999). J. Neurochem. 72, 2479–2487.

    Article  PubMed  Google Scholar 

  • Lustbader, J. W., Cirilli, M., Lin, C., Xu, H. W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., Trinchese, F., Liu, S., Gunn-Moore, F., Lue, L. F., Walker, D. G., Kuppusamy, P., Zewier, Z. L., Arancio, O., Stern, D., Yan, S. S. and Wu, H. (2004). Science 304, 448–452.

    Article  PubMed  Google Scholar 

  • Mancuso, M., Filosto, M., Bosetti, F., Ceravolo, R., Rocchi, A., Tognoni, G., Manca, M. L., Solaini, G., Siciliano, G., and Murri, L. (2003). Exp. Neurol. 182, 421–426.

    Article  PubMed  Google Scholar 

  • May, P. C., Gitter, B. D., Waters, D. C., Simmons, L. K., Becker, G. W., Small, J. S., and Robison, P. M. (1992). Neurobiol. Aging 13, 605–607.

    Article  PubMed  Google Scholar 

  • Mecocci, P., Cherubini, A., Beal, M. F., Cecchetti, R., Chionne, F., Polidori, M. C., Romano, G., and Senin, U. (1996). Neurosci. Lett. 207, 129–132.

    Article  PubMed  Google Scholar 

  • Moreira, P. I., Santos, M. S., Moreno, A., Rego, A. C., and Oliveira, C. (2002). J. Neurosci. Res. 69, 257–267.

    Article  PubMed  Google Scholar 

  • Moreira, P. I., Santos, M. S., Moreno, A. M., Seica, R., and Oliveira, C. R. (2003). Diabetes 52, 1449–1456.

    PubMed  Google Scholar 

  • Muller, W. E., Kirsch, C., and Eckert, G. P. (2001). Biochem. Soc. Trans. 29, 617–623.

    Article  PubMed  Google Scholar 

  • Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y. and LaFerla, F. M. (2003). Neuron 39, 409–421.

    Article  PubMed  Google Scholar 

  • Panov, A. V., Gutekunst, C. A., Leavitt, B. R., Hayden, M. R., Burke, J. R., Strittmatter, W. J., and Greenamyre, J. T. (2002). Nat. Neurosci. 5, 731–736.

    PubMed  Google Scholar 

  • Parker, W. D., Jr. (1991). Ann. N.Y. Acad. Sci. 640, 59–64.

    PubMed  Google Scholar 

  • Penefsky, H. S. (1985). Proc. Natl. Acad. Sci. U.S.A. 82, 1589–1593.

    PubMed  Google Scholar 

  • Pereira, C., Santos, M. S., and Oliveira, C. (1998). Neuroreport 9, 1749–1755.

    PubMed  Google Scholar 

  • Pereira, C., Santos, M. S., and Oliveira, C. (1999). Neurobiol. Dis. 6, 209–219.

    Article  PubMed  Google Scholar 

  • Petanceska, S. S., Seeger, M., Checler, F., and Gandy, S. (2000). J. Neurochem. 74, 1878–1884.

    Article  PubMed  Google Scholar 

  • Rossignol, R., Faustin, B., Rocher, C., Malgat, M., Mazat, J. P., and Letellier, T. (2003). Biochem. J. 370, 751–762.

    Article  PubMed  Google Scholar 

  • Rossignol, R., Letellier, T., Malgat, M., Rocher, C., and Mazat, J. P. (2000). Biochem. J. 347(Pt. 1), 45–53.

    Article  PubMed  Google Scholar 

  • Rossignol, R., Malgat, M., Mazat, J. P., and Letellier, T. (1999). J. Biol. Chem. 274, 33426–33432.

    Article  PubMed  Google Scholar 

  • Schwerzmann, K., Cruz-Orive, L. M., Eggman, R., Sanger, A., and Weibel, E. R. (1986). J. Cell Biol. 102, 97–103.

    Article  PubMed  Google Scholar 

  • Scorrano, L., Ashiya, M., Buttle, K., Weiler, S., Oakes, S. A., Mannella, C. A., and Korsmeyer, S. J. (2002). Dev. Cell 2, 55–67.

    Article  PubMed  Google Scholar 

  • Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schlossmacher, M., Whaley, J., Swindlehurst, C. and et al. (1992). Nature 359, 325–327.

    Article  PubMed  Google Scholar 

  • Shoffner, J. M. (1997). Neurogenetics 1, 13–19.

    Article  PubMed  Google Scholar 

  • Sipos, I., Tretter, L., and Adam-Vizi, V. (2003). J. Neurochem. 84, 112–118.

    Article  PubMed  Google Scholar 

  • Skovronsky, D. M., Doms, R. W., and Lee, V. M. (1998). J. Cell Biol. 141, 1031–1039.

    Article  PubMed  Google Scholar 

  • Solaini, G., Baracca, A., Parenti Castelli, G. and Lenaz, G. (1984). J. Bioenerg. Biomembr. 16, 391–406.

    Article  PubMed  Google Scholar 

  • Takahashi, R. H., Milner, T. A., Li, F., Nam, E. E., Edgar, M. A., Yamaguchi, H., Beal, M. F., Xu, H., Greengard, P., and Gouras, G. K. (2002). Am. J. Pathol. 161, 1869–1879.

    PubMed  Google Scholar 

  • Trimmer, P. A., Swerdlow, R. H., Parks, J. K., Keeney, P., Bennett, J. P., Jr., Miller, S. W., Davis, R. E., and Parker, W. D., Jr. (2000). Exp. Neurol. 162, 37–50.

    Article  PubMed  Google Scholar 

  • Turner, R. S., Suzuki, N., Chyung, A. S., Younkin, S. G., and Lee, V. M. (1996). J. Biol. Chem. 271, 8966–8970.

    Article  PubMed  Google Scholar 

  • Vijayasarathy, C., Biunno, I., Lenka, N., Yang, M., Basu, A., Hall, I. P., and Avadhani, N. G. (1998). Biochim. Biophys. Acta 1371, 71–82.

    PubMed  Google Scholar 

  • Waschuk, S. A., Elton, E. A., Darabie, A. A., Fraser, P. E., and McLaurin, J. A. (2001). J. Biol. Chem. 276, 33561–33568.

    Article  PubMed  Google Scholar 

  • Wirths, O., Multhaup, G., Czech, C., Blanchard, V., Moussaoui, S., Tremp, G., Pradier, L., Beyreuther, K., and Bayer, T. A. (2001). Neurosci. Lett. 306, 116–120.

    Article  PubMed  Google Scholar 

  • Zhang, Y., McLaughlin, R., Goodyer, C. and LeBlanc, A. (2002). J. Cell Biol. 156, 519–529.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Scuola Superiore Sant’Anna, Piazza Martiri della libertà 33, Pisa, Italy

    A. M. Aleardi & G. C. Solaini

  2. INSERM, U688 Physiopathologie Mitochondriale, Université Victor Segalen-Bordeaux 2, Bordeaux, France

    A. M. Aleardi, G. Benard, O. Augereau, M. Malgat, J. P. Mazat, T. Letellier, J. Dachary-Prigent & R. Rossignol

  3. Institut de Biochimie et Génétique Cellulaires du Centre National de la Recherche Scientifique, UMR5095, Université Victor Segalen Bordeaux 2, Bordeaux, France

    J. C. Talbot

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  1. A. M. Aleardi
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  2. G. Benard
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  3. O. Augereau
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  9. G. C. Solaini
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  10. R. Rossignol
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Correspondence to R. Rossignol.

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Aleardi, A.M., Benard, G., Augereau, O. et al. Gradual Alteration of Mitochondrial Structure and Function by β-Amyloids: Importance of Membrane Viscosity Changes, Energy Deprivation, Reactive Oxygen Species Production, and Cytochrome c Release. J Bioenerg Biomembr 37, 207–225 (2005). https://doi.org/10.1007/s10863-005-6631-3

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