Although synaptic endo- and exocytosis are thought to depend on local ATP, neurotransmission in response to slow stimulation was fairly normal in drp1 synapses. But under high frequency stimulation—such as occurs during muscle contractions—synapses at drp1 neuromuscular junctions (NMJs) ran out of steam.
The failure stemmed from an inability of drp1 synapses to mobilize reserve pool (RP) vesicles, which sit back from the membrane until they are called upon during strong stimulations. “It's a surprisingly specific defect,” says Bellen. “[Cytoplasmic] glycolysis must be sufficient, except when energy is in high demand.” By providing this energy in the form of ATP, the authors were able to partially restore drp1 neurotransmission.
RP vesicles might be moved by myosin, since myosin inhibitors blocked this ATP-mediated rescue. “A vesicle,” says Bellen, “is a pretty large object to drag through the cytoplasm at high speeds. It makes sense in retrospect that this requires the most energy.”