文章基本信息

标题：Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids
本地全文：下载
作者：Kalimuthusamy Natarajaseenivasan ; Alvaro Garcia ; Prema Velusamy 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：11
页码：1-21
DOI：10.1016/j.isci.2022.105407
语种：English
出版社：Elsevier
摘要：SummaryDisturbances 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.Graphical abstractDisplay OmittedHighlights•Astrocyte-neuron metabolic coupling maintains brain lipid homeostasis•Neurons are highly sensitive to toxic peroxidated fatty acids (pFA)•Accumulation of pFA in neurons induces autophagy and release of pFA•Citrate shuttling in astrocytes is required to process excess neuron-derived pFANeuroscience; Cellular neuroscience; Cell biology