The function of mitochondria in presynaptic development at the neuromuscular junction.
Mitochondria with high membrane potential (DeltaPsi(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 DeltaPsi(m) and the development of synaptic specializations. Using mitochondrial DeltaPsi(m)-sensitive probe JC-1, we found that DeltaPsi(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 DeltaPsi(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(+)/Ca(2+) 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.
Lee
Chi Wai
CW
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Peng
H Benjamin
HB
D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D003401:Creatine / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008863:Microspheres; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D014981:Xenopus
D000199:Actins; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000255:Adenosine Triphosphate; D003401:Creatine