The Function of Mitochondria in Presynaptic Development at the Neuromuscular Junction

Chi Wai Lee ${dagger}$ and H. Benjamin Peng

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

Monitoring Editor: Thomas Pollard

Mitochondria with high membranepotential ( ${Delta}$ ${Psi}$ _m) are enriched in the presynaptic nerve terminalat vertebrate neuromuscular junctions, but the exact functionof these localized synaptic mitochondria remains unclear. Here,we investigated the correlation between mitochondrial ${Delta}$ ${Psi}$ _m andthe development of synaptic specializations. Using mitochondrial ${Delta}$ ${Psi}$ _m-sensitive probe JC-1, we found that ${Delta}$ ${Psi}$ _m in Xenopus spinal neuronscould be reversibly elevated by creatine and suppressed by FCCP.Along naïve neurites, preexisting synaptic vesicle (SV)clusters were positively correlated with mitochondrial ${Delta}$ ${Psi}$ _m, suggestinga potential regulatory role of mitochondrial activity in synaptogenesis.Indicating a specific role of mitochondrial activity in presynapticdevelopment, mitochondrial ATP synthase inhibitor oligomycin,but not mitochondrial Na⁺/Ca²⁺ exchanger inhibitor CGP-37157,inhibited the clustering of SVs induced by growth-factor coatedbeads. Local F-actin assembly induced along spinal neuritesby beads was suppressed by FCCP or oligomycin Our results suggestthat a key role of presynaptic mitochondria is to provide ATPfor the assembly of actin cytoskeleton involved in the assemblyof the presynaptic specialization including the clustering ofSVs 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)