Peri-nuclear clustering of mitochondria is triggered during aluminum maltolate induced apoptosis

David A. DeWitt, Jennifer A. Hurd, Nena Fox, Brigitte E. Townsend, Kathleen J.S. Griffioen, Othman Ghribi, John Savory

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Synapse loss and neuronal death are key features of Alzheimer's disease pathology. Disrupted axonal transport of mitochondria is a potential mechanism that could contribute to both. As the major producer of ATP in the cell, transport of mitochondria to the synapse is required for synapse maintenance. However, mitochondria also play an important role in the regulation of apoptosis. Investigation of aluminum (Al) maltolate induced apoptosis in human NT2 cells led us to explore the relationship between apoptosis related changes and the disruption of mitochondrial transport. Similar to that observed with tau over expression, NT2 cells exhibit peri-nuclear clustering of mitochondria following treatment with Al maltolate. Neuritic processes largely lacked mitochondria, except in axonal swellings. Similar, but more rapid results were observed following staurosporine administration, indicating that the clustering effect was not specific to Al maltolate. Organelle clustering and transport disruption preceded apoptosis. Incubation with the caspase inhibitor zVAD-FMK effectively blocked apoptosis, however failed to prevent organelle clustering. Thus, transport disruption is associated with the initiation, but not necessarily the completion of apoptosis. These results, together with observed transport defects and apoptosis related changes in Alzheimer disease brain suggest that mitochondrial transport disruption may play a significant role in synapse loss and thus the pathogenesis or Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)195-205
Number of pages11
JournalJournal of Alzheimer's Disease
Issue number2
StatePublished - 2006
Externally publishedYes


  • Aluminum
  • Alzheimer's disease
  • Apoptosis
  • Axonal transport
  • Staurosporine

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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