Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 41, Pages 9507-9514Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0868-05.2005
Keywords
green fluorescent protein; organelle transport; signal transduction; wortmannin; mitochondrial membrane potential; oxidative stress
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Funding
- NINDS NIH HHS [NS34138] Funding Source: Medline
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Mitochondria have been identified as targets of the neurotoxic actions of zinc, possibly through decreased mitochondrial energy production and increased reactive oxygen species accumulation. It has been hypothesized that impairment of mitochondrial trafficking may be a mechanism of neuronal injury. Here, we report that elevated intraneuronal zinc impairs mitochondrial trafficking. At concentrations just sufficient to cause injury, zinc rapidly inhibited mitochondrial movement without altering morphology. Zinc chelation initially restored movement, but the actions of zinc became insensitive to chelator in < 10 min. A search for downstream signaling events revealed that inhibitors of phosphatidylinositol ( PI) 3-kinase prevented this zinc effect on movement. Moreover, transient inhibition of PI 3-kinase afforded neuroprotection against zinc-mediated toxicity. These data illustrate a novel mechanism that regulates mitochondrial trafficking in neurons and also suggest that mitochondrial trafficking may be closely coupled to neuronal viability.
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