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Vol. 19, Issue 1, 150-158, January 2008

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The Function of Mitochondria in Presynaptic Development at the Neuromuscular Junction

Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China

Submitted May 31, 2007; Revised October 4, 2007; Accepted October 10, 2007
Monitoring Editor: Thomas Pollard

Mitochondria with high membrane potential (_m) are enriched in the presynaptic nerve terminal at vertebrate neuromuscular junctions, but the exact function of these localized synaptic mitochondria remains unclear. Here, we investigated the correlation between mitochondrial _m and the development of synaptic specializations. Using mitochondrial _m-sensitive probe JC-1, we found that _m in Xenopus spinal neurons could be reversibly elevated by creatine and suppressed by FCCP. Along naïve neurites, preexisting synaptic vesicle (SV) clusters were positively correlated with mitochondrial _m, suggesting a potential regulatory role of mitochondrial activity in synaptogenesis. Indicating a specific role of mitochondrial activity in presynaptic development, mitochondrial ATP synthase inhibitor oligomycin, but not mitochondrial Na⁺/Ca²⁺ exchanger inhibitor CGP-37157, inhibited the clustering of SVs induced by growth factor–coated beads. Local F-actin assembly induced along spinal neurites by beads was suppressed by FCCP or oligomycin. Our results suggest that a key role of presynaptic mitochondria is to provide ATP for the assembly of actin cytoskeleton involved in the assembly of the presynaptic specialization including the clustering of SVs and mitochondria themselves.

*Present address: Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854.

Address correspondence to: H. Benjamin Peng (penghb{at}ust.hk)