Autophagocytosis of mitochondria is prominent in Alzheimer disease

Paula I. Moreira, Sandra L. Siedlak, Xinglong Wang, Maria S. Santos, Catarina R. Oliveira, Massimo Tabaton, Akihiko Nunomura, Luke I. Szweda, Gjumrakch Aliev, Mark A. Smith, Xiongwei Zhu, George Perry

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Mitochondrial abnormalities are prominent in Alzheimer disease. In this study, 2 mitochondrial markers, cytochrome oxidase-1 and lipoic acid, a sulfur-containing cofactor required for the activity of several mitochondrial enzyme complexes, were compared using light and electron microscopic analyses and immunoblot assays. Both lipoic acid and cytochrome oxidase-1 immunoreactivity are increased in the cytoplasm of pyramidal neurons in Alzheimer disease compared with control cases. Of significance, lipoic acid was found to be strongly associated with granular structures, and ultrastructure analysis showed localization to mitochondria, cytosol, and, importantly, in organelles identified as autophagic vacuoles and lipofuscin in Alzheimer disease but not control cases. Cytochrome oxidase-1 immunoreactivity was limited to mitochondria and cytosol in both Alzheimer and control cases. These data suggest that mitochondria are key targets of increased autophagic degradation in Alzheimer disease. Whether increased autophagocytosis is a consequence of an increased turnover of mitochondria or whether the mitochondria in Alzheimer disease are more susceptible to autophagy remains to be resolved.

Original languageEnglish (US)
Pages (from-to)525-532
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume66
Issue number6
DOIs
StatePublished - Jun 1 2007

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Keywords

  • Cytochrome oxidase-1
  • Immunoelectron microscopy
  • Lipoic acid
  • Proteolysis
  • Pyruvate dehydrogenase
  • Ultrastructure
  • α-Ketoglutarate dehydrogenase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Moreira, P. I., Siedlak, S. L., Wang, X., Santos, M. S., Oliveira, C. R., Tabaton, M., Nunomura, A., Szweda, L. I., Aliev, G., Smith, M. A., Zhu, X., & Perry, G. (2007). Autophagocytosis of mitochondria is prominent in Alzheimer disease. Journal of Neuropathology and Experimental Neurology, 66(6), 525-532. https://doi.org/10.1097/01.jnen.0000240476.73532.b0