Aerobic glycolysis is the predominant means of glucose metabolism in neuronal somata, which protects against oxidative damage
Open accessAbstract
It is generally thought that under basal conditions, neurons produce ATP mainly through mitochondrial oxidative phosphorylation (OXPHOS), and glycolytic activity only predominates when neurons are activated and need to meet higher energy demands. However, it remains unknown whether there are differences in glucose metabolism between neuronal somata and axon terminals. Here, we demonstrated that neuronal somata perform higher levels of aerobic glycolysis and lower levels of OXPHOS than terminals, both during basal and activated states. We found that the glycolytic enzyme pyruvate kinase 2 (PKM2) is localized predominantly in the somata rather than in the terminals. Deletion of Pkm2 in mice results in a switch from aerobic glycolysis to OXPHOS in neuronal somata, leading to oxidative damage and progressive loss of dopaminergic neurons. Our findings update the conventional view that neurons uniformly use OXPHOS under basal conditions and highlight the important role of somatic aerobic glycolysis in maintaining antioxidant capacity.
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Neurons predominantly use OXPHOS for ATP production under basal conditions and switch to glycolysis when facing increased energy needs.
“Neurons predominantly use OXPHOS for ATP production under basal conditions and just switch to glycolysis when facing increased energy needs [24].”
From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [24]
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“Excessive ROS can oxidize lipids, proteins and nucleic acids, resulting in irreversible damage to neurons 9,10 .”
BackgroundA Cellular Perspective on Brain Energy Metabolism and Functional Imaging
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“Previous work reported that neurons switch from aerobic glycolysis to OXPHOS during early development 54 , and, compared to the adult hippocampus, the juvenile hippocampus has increased glucose metabolism via the TCA cycle 55 .”
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APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons
Budny, V., Knöpfli, Y., Meier, D., Zürcher, K., Bodenmann, C., Peter, S. L., Müller, T., Tardy, M., Cortijo, C., & Tackenberg, C. (2024) · Cells · doi:10.3390/cells13141207 · Cited by 15 · see citing works
- Authors
- Wei, Y., Miao, Q., Zhang, Q., Mao, S., Li, M., Xu, X., Xia, X., Wei, K., Fan, Y., Zheng, X., Fang, Y., Mei, M., Zhang, Q., Ding, J., Fan, Y., Lu, M., & Hu, G.
- Affiliations
- Nanjing Medical University (CN)
- Nanjing University of Chinese Medicine (CN)
- Corresponding author
- Hu, Gang
- Venue
- Nature Neuroscience
- Published
- 2023-11-23
- Volume
- 26
- Issue
- 12
- Pages
- 2081-2089
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W4388946931
- Cited by
- 153
- References
- 11
- Citations by year
- 2026: 47 · 2025: 64 · 2024: 42
- FWCI
- 18.87
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Mendeley Data (cc-by)
- Mendeley Data
- Funders
- National Natural Science Foundation of China (No.81991523, No.82073823)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- aerobic glycolysis, oxidative phosphorylation, neuronal somata, axon terminals, PKM2, dopaminergic neurons, oxidative damage, neuronal energy metabolism
- MeSH terms
- Animals, Glucose, Glycolysis, Oxidative Phosphorylation, Phosphotransferases, Oxidative Stress, Mice
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