title: Glycolytic Enzymes Localize to Synapses under Energy Stress to Support Synaptic Function.
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.
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Department of Cell Biology and Department of Neuroscience, Yale University School of Medicine, P.O. Box 9812, New Haven, CT 06536-0812, USA.
authors.forename: SoRi
authors.initials: S
authors.lastname: Jang
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Department of Cell Biology and Department of Neuroscience, Yale University School of Medicine, P.O. Box 9812, New Haven, CT 06536-0812, USA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Nelson
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Bend
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Department of Cell Biology and Department of Neuroscience, Yale University School of Medicine, P.O. Box 9812, New Haven, CT 06536-0812, USA.
authors.forename: Lucelenie
authors.initials: L
authors.lastname: Rodríguez-Laureano
authors.affiliation: Laboratorio de Microbiología, Facultad de Ciencias Biológicas, Universidad Ricardo Palma, P.O. Box 1801, Lima 33, Perú
authors.forename: Felipe G
authors.initials: FG
authors.lastname: Tueros
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Department of Cell Biology and Department of Neuroscience, Yale University School of Medicine, P.O. Box 9812, New Haven, CT 06536-0812, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Cartagenova
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Department of Cell Biology and Department of Neuroscience, Yale University School of Medicine, P.O. Box 9812, New Haven, CT 06536-0812, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Underwood
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Erik M
authors.initials: EM
authors.lastname: Jorgensen
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Department of Cell Biology and Department of Neuroscience, Yale University School of Medicine, P.O. Box 9812, New Haven, CT 06536-0812, USA; Instituto de Neurobiología, Recinto de Ciencias Médicas, Universidad de Puerto Rico, 201 Boulevard del Valle, San Juan 00901, Puerto Rico. Electronic address: daniel.colon-ramos@yale.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Colón-Ramos
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D004705:Endocytosis; D000860:Hypoxia; D055432:Metabolomics; D009154:Mutation; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology*; D013312:Stress, Physiological; D013572:Synaptic Vesicles / Q000201:enzymology / Q000378:metabolism
chemical_list: D010732:Phosphofructokinase-1