Glial glycolysis is essential for neuronal survival in Drosophila
Open accessAbstract
Neuronal information processing requires a large amount of energy, indicating that sugars and other metabolites must be efficiently delivered. However, reliable neuronal function also depends on the maintenance of a constant microenvironment in the brain. Therefore, neurons are efficiently separated from circulation by the blood-brain barrier, and their long axons are insulated by glial processes. At the example of the Drosophila brain, we addressed how sugar is shuttled across the barrier to nurture neurons. We show that glial cells of the blood-brain barrier specifically take up sugars and that their metabolism relies on glycolysis, which, surprisingly, is dispensable in neurons. Glial cells secrete alanine and lactate to fuel neuronal mitochondria, and lack of glial glycolysis specifically in the adult brain causes neurodegeneration. Our work implies that a global metabolic compartmentalization and coupling of neurons and glial cells is a conserved, fundamental feature of bilaterian nervous systems independent of their size.
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In Drosophila melanogaster, glycolysis appears to be more essential in glial cells than it is in neurons.
“In Drosophila melanogaster, glycolysis appears to be more essential in glial cells than it is in neurons; knockdown of glycolytic enzymes in neurons did not affect the viability or the general behavior of flies, whereas knockdown in glial cells produced noticeable phenotypic changes (Volkenhoff et al., 2015).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Volkenhoff et al., 2015
Knockdown of glycolytic enzymes in Drosophila neurons did not affect the viability or the general behavior of flies.
“In Drosophila melanogaster, glycolysis appears to be more essential in glial cells than it is in neurons; knockdown of glycolytic enzymes in neurons did not affect the viability or the general behavior of flies, whereas knockdown in glial cells produced noticeable phenotypic changes (Volkenhoff et al., 2015).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Volkenhoff et al., 2015
Knockdown of glycolytic enzymes in Drosophila glial cells produced noticeable phenotypic changes.
“In Drosophila melanogaster, glycolysis appears to be more essential in glial cells than it is in neurons; knockdown of glycolytic enzymes in neurons did not affect the viability or the general behavior of flies, whereas knockdown in glial cells produced noticeable phenotypic changes (Volkenhoff et al., 2015).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Volkenhoff et al., 2015
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- Authors
- Volkenhoff, A., Weiler, A., Letzel, M., Stehling, M., Klämbt, C., & Schirmeier, S.
- Affiliations
- University of Münster (DE)
- Max Planck Institute for Molecular Biomedicine (DE)
- Corresponding author
- Schirmeier, Stefanie
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 22
- Issue
- 3
- Pages
- 437-447
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1921252690
- Cited by
- 339
- References
- 64
- Citations by year
- 2026: 25 · 2025: 42 · 2024: 38 · 2023: 41 · 2022: 33 · 2021: 32 · 2020: 38 · 2019: 16 · 2018: 33 · 2017: 27 · 2016: 11 · 2015: 3
- FWCI
- 11.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- blood-brain barrier, neuronal survival, Drosophila brain, glial cells, sugar transport, lactate secretion, neurodegeneration, brain energy metabolism
- MeSH terms
- Alanine, Animals, Blood-Brain Barrier, Cell Survival, Drosophila, Energy Metabolism, Female, Glycolysis, Locomotion, Neuroglia, Neurons, Trehalose, Lactic Acid
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