Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids
Summary: Disturbances in lipid metabolism in the CNS contribute to neurodegeneration and cognitive impairments. Through tight metabolic coupling, astrocytes provide energy to neurons by delivering lactate and cholesterol and by taking up and processing neuron-derived peroxidated fatty acids (pFA). D...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222016790 |
| _version_ | 1797984455173865472 |
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| author | Kalimuthusamy Natarajaseenivasan Alvaro Garcia Prema Velusamy Santhanam Shanmughapriya Dianne Langford |
| author_facet | Kalimuthusamy Natarajaseenivasan Alvaro Garcia Prema Velusamy Santhanam Shanmughapriya Dianne Langford |
| author_sort | Kalimuthusamy Natarajaseenivasan |
| collection | DOAJ |
| description | Summary: Disturbances in lipid metabolism in the CNS contribute to neurodegeneration and cognitive impairments. Through tight metabolic coupling, astrocytes provide energy to neurons by delivering lactate and cholesterol and by taking up and processing neuron-derived peroxidated fatty acids (pFA). Disruption of CNS lipid homeostasis is observed in people who use cocaine and in several neurodegenerative disorders, including HIV. The brain’s main source of energy is aerobic glycolysis, but numerous studies report a switch to β-oxidation of FAs in response to cocaine. Unlike astrocytes, in response to cocaine, neurons cannot efficiently consume excess pFAs for energy. Accumulation of pFA in neurons induces autophagy and release of pFA. Astrocytes endocytose the pFA for oxidation as an energy source. Our data show that blocking mitochondrial/cytosolic citrate transport reduces the neurotrophic capacity of astrocytes, leading to decreased neuronal fitness. |
| first_indexed | 2024-04-11T07:01:58Z |
| format | Article |
| id | doaj.art-18d2f0dd96484264b3ecd863df479861 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T07:01:58Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-18d2f0dd96484264b3ecd863df4798612022-12-22T04:38:36ZengElsevieriScience2589-00422022-11-012511105407Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acidsKalimuthusamy Natarajaseenivasan0Alvaro Garcia1Prema Velusamy2Santhanam Shanmughapriya3Dianne Langford4Department of Neural Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; Department of Microbiology, Bharathidasan University, Tiruchirapalli, IndiaDepartment of Neural Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USAHeart and Vascular Institute, Department of Medicine, Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey, PA, USAHeart and Vascular Institute, Department of Medicine, Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey, PA, USADepartment of Neural Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; Corresponding authorSummary: Disturbances in lipid metabolism in the CNS contribute to neurodegeneration and cognitive impairments. Through tight metabolic coupling, astrocytes provide energy to neurons by delivering lactate and cholesterol and by taking up and processing neuron-derived peroxidated fatty acids (pFA). Disruption of CNS lipid homeostasis is observed in people who use cocaine and in several neurodegenerative disorders, including HIV. The brain’s main source of energy is aerobic glycolysis, but numerous studies report a switch to β-oxidation of FAs in response to cocaine. Unlike astrocytes, in response to cocaine, neurons cannot efficiently consume excess pFAs for energy. Accumulation of pFA in neurons induces autophagy and release of pFA. Astrocytes endocytose the pFA for oxidation as an energy source. Our data show that blocking mitochondrial/cytosolic citrate transport reduces the neurotrophic capacity of astrocytes, leading to decreased neuronal fitness.http://www.sciencedirect.com/science/article/pii/S2589004222016790NeuroscienceCellular neuroscienceCell biology |
| spellingShingle | Kalimuthusamy Natarajaseenivasan Alvaro Garcia Prema Velusamy Santhanam Shanmughapriya Dianne Langford Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids iScience Neuroscience Cellular neuroscience Cell biology |
| title | Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids |
| title_full | Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids |
| title_fullStr | Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids |
| title_full_unstemmed | Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids |
| title_short | Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids |
| title_sort | citrate shuttling in astrocytes is required for processing cocaine induced neuron derived excess peroxidated fatty acids |
| topic | Neuroscience Cellular neuroscience Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222016790 |
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