Glycolytic enzymes localize to synapses under energy stress to support synaptic function
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Abstract
Changes in neuronal activity create local and transient changes in energy demands at synapses. Here we discover a metabolic compartment that forms in vivo near synapses to meet local energy demands and support synaptic function in Caenorhabditis elegans neurons. Under conditions of energy stress, glycolytic enzymes redistribute from a diffuse localization in the cytoplasm to a punctate localization adjacent to synapses. Glycolytic enzymes colocalize, suggesting the ad hoc formation of a glycolysis compartment, or a "glycolytic metabolon," that can maintain local levels of ATP. Local formation of the glycolytic metabolon is dependent on presynaptic scaffolding proteins, and disruption of the glycolytic metabolon blocks the synaptic vesicle cycle, impairs synaptic recovery, and affects locomotion. Our studies indicate that under energy stress conditions, energy demands in C. elegans synapses are met locally through the assembly of a glycolytic metabolon to sustain synaptic function and behavior. VIDEO ABSTRACT.
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Substantial direct metabolism of glucose in presynaptic terminals is consistent with an important role for glucose transporters and glycolysis in presynaptic terminals.
“consistent with an important role for glucose transporters and glycolysis in presynaptic terminals (Jang et al., 2016; Ashrafi et al., 2017; Ashrafi and Ryan, 2017).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Jang et al., 2016
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- Authors
- Jang, S., Nelson, J. C., Bend, E. G., Rodríguez-Laureano, L., Tueros, F. G., Cartagenova, L., Underwood, K., Jorgensen, E. M., & Colón-Ramos, D. A.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Universidad Ricardo Palma (PE)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 90
- Issue
- 2
- Pages
- 278-291
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4840048
- OpenAlex
- W2334665931
- Cited by
- 270
- References
- 89
- Citations by year
- 2026: 23 · 2025: 20 · 2024: 29 · 2023: 24 · 2022: 32 · 2021: 27 · 2020: 23 · 2019: 25 · 2018: 32 · 2017: 23 · 2016: 11
- FWCI
- 17.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (P40 OD010440, R01 NS034307)
- Mitani lab
- Klingenstein Foundation
- Alfred P. Sloan Foundation
- March of Dimes Research
- NSF (0920069)
- Cellular, Biochemical, and Molecular Sciences Predoctoral Training Program (T32 GM007223)
- Universidad Ricardo Palma, Perú
- Research Experience for Peruvian Undergraduates (REPU) program
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- energy stress, ATP production, synaptic vesicle recycling, synaptic recovery, locomotion, Caenorhabditis elegans neurons
- MeSH terms
- Animals, Hypoxia, Endocytosis, Mutation, Phosphofructokinase-1, Stress, Physiological, Synaptic Vesicles, Caenorhabditis elegans, Presynaptic Terminals, Metabolomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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