Synaptic Mitochondria Are Critical for Mobilization of Reserve Pool Vesicles at Drosophila Neuromuscular Junctions
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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.
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A part of glutamate can be taken up by mitochondria, where it is metabolized to 2-oxoglutarate, contributing to ATP synthesis.
“A part of the glutamate can be taken up by the mitochondria, where it is metabolized to 2-oxoglutarate further contributing to the synthesis of ATP (Tang and Zucker, 1997; Verstreken et al., 2005), thereby removing it from the glutamine–glutamate cycle and reducing its toxicity (Vaglio-Garro et al., 2024b).”
From Toxic Concentrations of Glutamate Induce Ferroptosis without Affecting Mitochondrial Respiration in Rodent Brain Slice Cultures (2026) · cites this paper as Verstreken et al., 2005
The Discussion reports ATP generation by synaptic mitochondria, supporting the ATP-production part of the claim. Our copy does not say that mitochondria take up glutamate or metabolize it to 2-oxoglutarate (searched both terms and a paraphrase), so it does not establish the claimed route to ATP synthesis. (LLM, conf=0.83)
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- Authors
- Verstreken, P., Ly, C. V., Venken, K. J. T., Koh, T.-W., Zhou, Y., & Bellen, H. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Baylor College of Medicine (US)
- Corresponding author
- Bellen, Hugo J.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2005-08
- Volume
- 47
- Issue
- 3
- Pages
- 365-378
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1974750801
- Cited by
- 841
- References
- 1
- Citations by year
- 2026: 23 · 2025: 45 · 2024: 42 · 2023: 41 · 2022: 29 · 2021: 46 · 2020: 44 · 2019: 32 · 2018: 44 · 2017: 40 · 2016: 53 · 2015: 37 · 2014: 40 · 2013: 41 · 2012: 46
- FWCI
- 14.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Funders
- Cold Spring Harbor Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- synaptic mitochondria, Drp1, Drosophila neuromuscular junction, neurotransmission, mitochondrial ATP production, protein kinase A signaling, myosin, synaptic efficacy, mitochondrial distribution
- MeSH terms
- Animals, Calcium, Cytoskeletal Proteins, Drosophila, Electric Stimulation, Endocytosis, Larva, Membrane Proteins, Mitochondria, Mutation, Myosins, Synaptic Transmission, Neuromuscular Junction, Neuropeptides, Synapses, Synaptic Vesicles, Tissue Distribution, Presynaptic Terminals, Cyclic AMP-Dependent Protein Kinases, Neurotransmitter Agents, Myosin Light Chains, GTP-Binding Proteins, GTP Phosphohydrolases, Drosophila Proteins, Vesicular Transport Proteins
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