Synaptic Mitochondria Are Critical for Mobilization of Reserve Pool Vesicles at Drosophila Neuromuscular Junctions

• Published in: Neuron (Cambridge, Mass.) Vol. 47; no. 3; pp. 365 - 378
• Main Authors: Verstreken, Patrik, Ly, Cindy V., Venken, Koen J.T., Koh, Tong-Wey, Zhou, Yi, Bellen, Hugo J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.08.2005; Elsevier Limited
• Subjects: Animals; Calcium - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Cytoskeletal Proteins; Defects; Drosophila; 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; Insects; Larva; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microscopy; Mitochondria; 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; Proteins; Synapses - metabolism; Synapses - physiology; Synaptic Transmission; Synaptic Vesicles - physiology; Tissue Distribution; Vesicular Transport Proteins
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2005.06.018

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 Ca 2+ 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.