Local power for synapses

New results from Patrik Verstreken, Hugo Bellen, and colleagues (Baylor College of Medicine, Houston, TX) show that mitochondria in axon terminals provide energy to overwrought synapses.Being far from the cell body, synapses have their own reserve of cellular machinery, including ER and mitochondria. Bellen's group analyzed the contribution of local mitochondria to synaptic function using a fly dynamin-like mutant called drp1, which lacks mitochondria at the synapse but retains them in the cell body.

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.”

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