Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions.
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.
Verstreken
Patrik
P
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Ly
Cindy V
CV
Venken
Koen J T
KJ
Koh
Tong-Wey
TW
Zhou
Yi
Y
Bellen
Hugo J
HJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000302:isolation & purification / Q000502:physiology; D019204:GTP-Binding Proteins; D007814:Larva; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009154:Mutation; D018994:Myosin Light Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000502:physiology*; D014018:Tissue Distribution; D033921:Vesicular Transport Proteins
D003598:Cytoskeletal Proteins; C113692:Dap160 protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D018994:Myosin Light Chains; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D033921:Vesicular Transport Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; C504426:DRP1 protein, Drosophila; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D009218:Myosins; D002118:Calcium