Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids

Kalimuthusamy Natarajaseenivasan; Alvaro Garcia; Prema Velusamy; Santhanam Shanmughapriya; Dianne Langford

doi:10.1016/j.isci.2022.105407

Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids

iScience. 2022 Oct 20;25(11):105407. doi: 10.1016/j.isci.2022.105407. eCollection 2022 Nov 18.

Authors

Kalimuthusamy Natarajaseenivasan^{1

2}, Alvaro Garcia¹, Prema Velusamy³, Santhanam Shanmughapriya³, Dianne Langford¹

Affiliations

¹ Department of Neural Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
² Department of Microbiology, Bharathidasan University, Tiruchirapalli, India.
³ Heart and Vascular Institute, Department of Medicine, Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey, PA, USA.

Abstract

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.

Keywords: Cell biology; Cellular neuroscience; Neuroscience.

Abstract

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