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Glutamate decreases oxidative stress and lipid droplet formation in astrocytes
Abstract
Astrocytes degrade fatty acids in response to glutamate while reducing the abundance of lipid droplets. But how glutamate regulates lipid droplets in astrocytes is unclear. Here, we used primary rat astrocytes to show that glutamate decreases the amount of reactive oxygen species, which, in turn, reduces autophagy and the amount of lipids in need of storage in lipid droplets. This decrease in lipid droplets and reactive oxygen species occurs independently of glutamate import through excitatory amino acid transporters (EAATs). However, activation of AMPK, downstream of EAATs, further promotes a decrease in lipid droplets. Glutamate also increases the pool of fused mitochondria capable of maintaining enhanced fatty acid metabolism. Our work reveals how astrocytic metabolism is regulated by glutamate, which can serve to coordinate astrocyte physiology with neuronal activity.
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Lysosomal degradation is an important source of lipids to be stored in lipid droplets.
“Lysosomal degradation is an important source of lipids to be stored in lipid droplets 12,27 .”
From ApoE4 impairs astrocyte lipid droplet formation via endolysosomal dysfunction (2026) · cites this paper as [27]
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Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971
Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity
Ioannou, M. S., Jackson, J., Sheu, S.-H., Chang, C.-L., Weigel, A. V., Liu, H., Pasolli, H. A., Xu, C. S., Pang, S., Matthies, D., et al. (2019) · Cell · doi:10.1016/j.cell.2019.04.001 · Cited by 760 · cited 13×
“…of magnitude depending on the compartment and/or biological context (Dzubay and Jahr, 1999; Kalivas, 2011), 100 µM glutamate was used, as this concentration was previously shown to increase lipid transport from neurons to astrocytes and reduce astrocyte lipid droplets (Ioannou et al., 2019a).”
InfluentialSelf-citationApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism
Qi, G., Mi, Y., Shi, X., Gu, H., Brinton, R. D., & Yin, F. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108572 · Cited by 379
Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK
Li, Y., Munoz-Mayorga, D., Nie, Y., Kang, N., Tao, Y., Lagerwall, J., Pernaci, C., Curtin, G., Coufal, N. G., Mertens, J., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.03.014 · Cited by 160
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Research works printed but not linked: 40
- Bae, 2024, Neuronal AMPK regulates lipid transport to microglia, Trends Cell Biol., 34, 695, 10.1016/j.tcb.2024.08.001 · DOI
- Bonvento, 2021, Astrocyte-neuron metabolic cooperation shapes brain activity, Cell Metab., 33, 1546, 10.1016/j.cmet.2021.07.006 · DOI · Paper page
- Boone, 2000, Bimodal activation of Acetyl-CoA carboxylase by glutamate, J. Biol. Chem., 275, 10819, 10.1074/jbc.275.15.10819 · DOI
- Dzubay, 1999, The concentration of synaptically released glutamate outside of the climbing fiber–purkinje cell synaptic cleft, J. Neurosci., 19, 5265, 10.1523/JNEUROSCI.19-13-05265.1999 · DOI · Paper page
- Fecher, 2019, Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity, Nat. Neurosci., 22, 1731, 10.1038/s41593-019-0479-z · DOI
- Foo, 2011, Development of a method for the purification and culture of rodent astrocytes, Neuron, 71, 799, 10.1016/j.neuron.2011.07.022 · DOI · Paper page
- Francés, 2024, Diverting glial glycolytic flux towards neurons is a memory-relevant role of Drosophila CRH-like signalling, Nat. Commun., 15, 10467, 10.1038/s41467-024-54778-x · DOI
- Goodman, 2024, Glial lipid droplets resolve ROS during sleep, Nat. Neurosci., 27, 610, 10.1038/s41593-023-01546-7 · DOI
- Han, 2018, Isotope-labeling derivatization with 3-nitrophenylhydrazine for LC/multiple-reaction monitoring-mass-spectrometry-based quantitation of carnitines in dried blood spots, Anal. Chim. Acta, 1037, 177, 10.1016/j.aca.2018.01.045 · DOI
- Han, 2015, An isotope-labeled chemical derivatization method for the quantitation of short-chain fatty acids in human feces by liquid chromatography–tandem mass spectrometry, Anal. Chim. Acta, 854, 86, 10.1016/j.aca.2014.11.015 · DOI
- Haynes, 2024, A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis, Nat. Neurosci., 27, 666, 10.1038/s41593-023-01568-1 · DOI
- Hlozkova, 2024, Rewired glutamate metabolism diminishes cytostatic action of L-asparaginase, Cancer Lett., 605, 217242, 10.1016/j.canlet.2024.217242 · DOI
- Inloes, 2014, The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase, Proc. Natl Acad. Sci. USA, 111, 14924, 10.1073/pnas.1413706111 · DOI
- Ioannou, 2019, A neuron-glia co-culture system for studying intercellular lipid transport, Curr. Protoc. Cell Biol., 84, e95, 10.1002/cpcb.95 · DOI
- Jacquemyn, 2024, Driving factors of neuronal ferroptosis, Trends Cell Biol., 34, 535, 10.1016/j.tcb.2024.01.010 · DOI
- Kalivas, 2011, Extracellular glutamate: functional compartments operate in different concentration ranges, Front. Syst. Neurosci., 5, 94, 10.3389/fnsys.2011.00094 · DOI · Paper page
- Liu, 2015, Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration, Cell, 160, 177, 10.1016/J.CELL.2014.12.019 · DOI · Paper page
- Lord, 2020, SuperPlots: communicating reproducibility and variability in cell biology, J. Cell Biol., 219, e202001064, 10.1083/jcb.202001064 · DOI · Paper page
- Marinangeli, 2018, AMP-activated protein kinase is essential for the maintenance of energy levels during synaptic activation, IScience, 9, 1, 10.1016/j.isci.2018.10.006 · DOI
- Mauvezin, 2015, Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion, Autophagy, 11, 1437, 10.1080/15548627.2015.1066957 · DOI · Paper page
- McKenna, 2013, Glutamate Pays its own way in astrocytes, Front. Endocrinol., 4, 191, 10.3389/fendo.2013.00191 · DOI
- Mi, 2023, Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration, Nat. Metab., 5, 445, 10.1038/s42255-023-00756-4 · DOI · Paper page
- Park, 2023, Redefining the role of AMPK in autophagy and the energy stress response, Nat. Commun., 14, 2994, 10.1038/s41467-023-38401-z · DOI
- Prah, 2019, A novel serum free primary astrocyte culture method that mimic quiescent astrocyte phenotype, J. Neurosci. Methods, 320, 50, 10.1016/j.jneumeth.2019.03.013 · DOI
- Rambold, 2011, Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation, Proc. Natl. Acad. Sci. USA, 108, 10190, 10.1073/pnas.1107402108 · DOI
- Rambold, 2015, Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics, Dev. Cell, 32, 678, 10.1016/j.devcel.2015.01.029 · DOI · Paper page
- Rose, 2018, Astroglial glutamate signaling and uptake in the hippocampus, 17, 10.3389/fnmol.2017.00451 · DOI
- Schott, 2019, Lipid droplet size directs lipolysis and lipophagy catabolism in hepatocytes, J. Cell Biol., 218, 3320, 10.1083/jcb.201803153 · DOI · Paper page
- Schulze, 2020, Direct lysosome-based autophagy of lipid droplets in hepatocytes, Proc. Natl Acad. Sci. USA, 117, 32443, 10.1073/pnas.2011442117 · DOI
- Shoenhard, 2025, Coordinating the energetic strategy of glia and neurons for memory, Trends Neurosci., 48, 93, 10.1016/j.tins.2025.01.001 · DOI
- Singh, 2009, Autophagy regulates lipid metabolism, Nature, 458, 1131, 10.1038/nature07976 · DOI · Paper page
- Sun, 2013, Glutamate-dependent neuroglial calcium signaling differs between young and adult brain, Science, 339, 197, 10.1126/science.1226740 · DOI
- Todd, 2020, The regulation of astrocytic glutamate transporters in health and neurodegenerative diseases, Int. J. Mol. Sci., 21, 9607, 10.3390/ijms21249607 · DOI · Paper page
- Twig, 2008, Fission and selective fusion govern mitochondrial segregation and elimination by autophagy, EMBO J., 27, 433, 10.1038/sj.emboj.7601963 · DOI · Paper page
- Voss, 2015, AMPK activation affects glutamate metabolism in astrocytes, Neurochem. Res., 40, 2431, 10.1007/s11064-015-1558-5 · DOI
- Wang, 2022, Acetyl-CoA carboxylases and diseases, Front. Oncol., 12, 836058, 10.3389/fonc.2022.836058 · DOI
- Weightman Potter, 2019, Basal fatty acid oxidation increases after recurrent low glucose in human primary astrocytes, Diabetologia, 62, 187, 10.1007/s00125-018-4744-6 · DOI
- Xu, 2020, The implication of oxidative stress and AMPK-Nrf2 antioxidative signaling in pneumonia pathogenesis, Front. Endocrinol., 11, 400, 10.3389/fendo.2020.00400 · DOI
- Yun, 2014, AMP-activated protein kinase mediates the antioxidant effects of resveratrol through regulation of the transcription factor FoxO1, FEBS J., 281, 4421, 10.1111/febs.12949 · DOI
- Zeng, 2023, Inhibition of mGluR5 ameliorates lipid accumulation and inflammation in HepG2 cells, Biochem. Biophys. Res. Commun., 653, 1, 10.1016/j.bbrc.2023.02.033 · DOI
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ApoE4 impairs astrocyte lipid droplet formation via endolysosomal dysfunction
Ralhan, I., Bae, J.-Y., Lee, N. Y., Cai, W., Chang, J., Jarad, S., Gu, H., Zhang, D., & Ioannou, M. S. (2026) · doi:10.64898/2026.09.01.748585
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Metadata
- Authors
- Rubio-Atonal, L. F., Chang, J., Jacquemyn, J., Ralhan, I., Ilarraza, I., & Ioannou, M. S.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2025-10-01
- Volume
- 138
- Issue
- 19
- ISSN
- 0021-9533
- 1477-9137
- PMC
- PMC12539204
- Cited by
- 7
- References
- 4
- Language
- en
- Funders
- Natural Sciences and Engineering Research Council of Canada (2020-04047)
- Canada Research Chairs (2021-00027)
- Women and Children's Health Research Institute
- Canadian Institutes of Health Research (181551)
- University of Alberta
- EMBO (ALTF 120-2022)
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