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Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain

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Molecular and Chemical Neuropathology

Abstract

Oxidative damage on biological molecules has been proposed as a major cause of alterations observed in aging brain as well as in neurodegenerative diseases. In this study, we measured membrane fluidity in mitochondria extracted from three cerebral regions and cerebellum of Alzheimer disease (AD) patients and age-matched controls by means of fluorescence polarization technique. A significant reduction of mitochondrial membrane fluidity was found in AD, except in cerebellum. In controls, a decrease of membrane fluidity was observed along with age, and it was also related to the content of the oxidized nucleoside 8-hydroxy-2′-deoxyguanosine (OH8dG) in mitochondrial DNA (mtDNA). Alteration in membrane fluidity seems to be a result of lipid peroxidation, since it dramatically decreased when mitochondria were exposed to FeCl2 and H2O2. The parallel increase of viscosity in mitochondrial membrane and the amount of OH8dG in mtDNA is suggestive of a relationship between these biological markers of oxidative stress. These results provide further evidence that oxidative stress may play a role in the pathogenesis of AD.

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Authors and Affiliations

  1. Gerontology & Geriatrics, Department of Clinical Medicine, Pathology and Pharmacology, Perugia University, Perugia, Italy

    Patrizia Mecocci, Roberta Cecchetti, Maria Cristina Polidori, Antonio Cherubini, Giustina Romano & Umberto Senin

  2. Neurochemistry Lab, Neurology Service, Massachusetts General Hospital Harvard Medical School, Boston, MA

    M. Flint Beal

  3. Department of Medical Physics, Policlinico Monteluce, Perugia, Italy

    Fausto Chionne

  4. Institute of Biochemistry and Medical Chemistry, Perugia University, Perugia, Italy

    Luca Avellini

Authors
  1. Patrizia Mecocci
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  2. M. Flint Beal
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  9. Umberto Senin
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Mecocci, P., Beal, M.F., Cecchetti, R. et al. Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain. Molecular and Chemical Neuropathology 31, 53–64 (1997). https://doi.org/10.1007/BF02815160

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  • DOI: https://doi.org/10.1007/BF02815160

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