Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions

Patrik Verstreken, Cindy V. Ly, Koen J.T. Venken, Tong Wey Koh, Yi Zhou, Hugo J. Bellen

Research output: Contribution to journalArticlepeer-review

548 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)365-378
Number of pages14
JournalNeuron
Volume47
Issue number3
DOIs
StatePublished - Aug 4 2005
Externally publishedYes

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