Mechanisms of Mitochondria–Neurofilament Interactions

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neurofilament-phosphorylation
neurofilament-sidearms
axonal organelle motility
atomic force microscopy
JC-1
dynamic light scattering
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Wagner, Oliver I
Lifshitz, Jonathan
Linden, M.
McIntosh, T. K
Leterrier, Jean-François
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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.

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2003-10-08
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Reprinted from The Journal of Neuroscience, Volume 23, Number 27, October 2003, pages 9046-58. Publisher URL: http://www.jneurosci.org/cgi/content/full/23/27/9046
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