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Verstreken, P, Ly, CV, Venken, KJ, Koh, TW, Zhou, Y and Bellen, HJ (2005) Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 47:365-78
In a forward screen for genes affecting neurotransmission in Drosophila, we identified mutations in dynamin-related protein (drp1). DRP1 is required for proper cellular distribution of mitochondria, and in mutant neurons, mitochondria are largely absent from synapses, thus providing a genetic tool to assess the role of mitochondria at synapses. Although resting Ca2+ is elevated at drp1 NMJs, basal synaptic properties are barely affected. However, during intense stimulation, mutants fail to maintain normal neurotransmission. Surprisingly, FM1-43 labeling indicates normal exo- and endocytosis, but a specific inability to mobilize reserve pool vesicles, which is partially rescued by exogenous ATP. Using a variety of drugs, we provide evidence that reserve pool recruitment depends on mitochondrial ATP production downstream of PKA signaling and that mitochondrial ATP limits myosin-propelled mobilization of reserve pool vesicles. Our data suggest a specific role for mitochondria in regulating synaptic strength.
Animals; Calcium/metabolism; Cyclic AMP-Dependent Protein Kinases/metabolism; Cytoskeletal Proteins; Drosophila/growth & development; Drosophila/metabolism; Drosophila/physiology; Drosophila/ultrastructure; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Electric Stimulation/methods; Endocytosis; GTP Phosphohydrolases/isolation & purification; GTP Phosphohydrolases/physiology; GTP-Binding Proteins; Larva; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mitochondria/metabolism; Mitochondria/physiology; Mitochondria/ultrastructure; Mutation; Myosin Light Chains/metabolism; Myosins/metabolism; Neuromuscular Junction/metabolism; Neuromuscular Junction/physiology; Neuromuscular Junction/ultrastructure; Neuropeptides/genetics; Neuropeptides/metabolism; Neurotransmitter Agents/metabolism; Presynaptic Terminals/metabolism; Synapses/metabolism; Synapses/physiology; Synaptic Transmission; Synaptic Vesicles/physiology; Tissue Distribution; Vesicular Transport Proteins