Mechanisms of mitochondria-neurofilament interactions

O. I. Wagner, J. Lifshitz, P. A. Janmey, M. Linden, T. K. McIntosh, J. F. Leterrier

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

Mitochondria are localized to regions of the cell where ATP consumption is high and are dispersed according to changes in local energy needs. In addition to motion directed by molecular motors, mitochondrial distribution in neuronal cells appears to depend on the docking of mitochondria to microtubules and neurofilaments. We examined interactions between mitochondria and neurofilaments using fluorescence microscopy, dynamic light scattering, atomic force microscopy, and sedimentation assays. Mitochondria-neurofilament interactions depend on mitochondrial membrane potential, as revealed by staining with a membrane potential sensitive dye (JC-1) in the presence of substrates/ADP or uncouplers (valinomycin/carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone) and are affected by the phosphorylation status of neurofilaments and neurofilament sidearms. Antibodies against the neurofilament heavy subunit disrupt binding between mitochondria and neurofilaments, and isolated neurofilament sidearms alone interact with mitochondria, suggesting that they mediate the interactions between the two structures. These data suggest that specific and regulated mitochondrial-neurofilament interactions occur in situ and may contribute to the dynamic distribution of these organelles within the cytoplasm of neurons.

Original languageEnglish (US)
Pages (from-to)9046-9058
Number of pages13
JournalJournal of Neuroscience
Volume23
Issue number27
StatePublished - Oct 8 2003
Externally publishedYes

Keywords

  • Atomic force microscopy
  • Axonal organelle motility
  • Dynamic light scattering
  • JC-1
  • Neurofilament-phosphorylation
  • Neurofilament-sidearms

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Wagner, O. I., Lifshitz, J., Janmey, P. A., Linden, M., McIntosh, T. K., & Leterrier, J. F. (2003). Mechanisms of mitochondria-neurofilament interactions. Journal of Neuroscience, 23(27), 9046-9058.