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The Effect of Microtubule Polyamination on Axonal Mitochondrial Transport

Suzanne Xu Photo

Richard Montgomery High School (Maryland)

Synaptic Functions Section, NINDS, NIH

The neuron is a highly specialized cell, typically characterized by its extremely polarized state, multiple dendritic branches, and a single long axon. Neuronal microtubules are more stable than their non-neuronal counterparts, lending themselves to such functions as cytoskeletal-tracks for organelle transport and axon maintenance. Polyamination has recently been suggested as aiding in microtubule stability. The inhibition of polyamine synthesis was found to decrease the production of cold-insoluble tubulin in axons and lower microtubule stability. However, the physiological effect of polyamination-mediated microtubule stability has not been explored in depth. In this study, we transfected primary cultured hippocampal neurons with Dsred-Mito to label mitochondria, enabling us to examine any alterations in mitochondrial trafficking in live neurons. To reduce microtubule stability, we treated the neurons with 5 mM Difluoromethylornithine (DFMO), a specific, irreversible inhibitor of ornithine decarboxylase (ODC) which is a rate-limiting enzyme in polyamine biosynthesis. Our preliminary results from live-imaging analysis indicate that DFMO decreases axonal mitochondrial mobility bi-directionally. The neurons treated with DFMO display reduced mitochondrial motility within axons (16.85 ± 2.05%, n = 22) relative to control neurons (26.00 ± 3.31%, n = 18, p = 0.026, Student t test), suggesting that tubulin polyamination is necessary for proper axonal transport of mitochondria. Given that polyamine levels in the brain are reduced with age and diseases such as Alzheimer’s disease and that axonal transport is important for neuronal function, our findings may provide some insights into our understanding of aging and neurodegenerative diseases. (Supported by the Intramural Program of NINDS, NIH)

Last Modified November 27, 2013