Astrocytic metabolic switch is a novel etiology for Cocaine and HIV-1 Tat-mediated neurotoxicity.

ABSTRACT: Calcium (Ca²⁺) dynamics and oxidative signaling control mitochondrial bioenergetics in the central nervous system, where astrocytes are a major energy source for neurons. Cocaine use exacerbates HIV-associated neurocognitive disorders, but little is known about disruptions in astrocyte metabolism in this context. Our data show that the HIV protein Tat and cocaine induce a metabolic switch from glucose to fatty acid oxidation in astrocytes, thereby limiting lactate transport to neurons. Mechanistic analyses revealed increased Mitochondrial Ca²⁺ Uniporter (MCU)-mediated Ca²⁺ uptake in astrocytes exposed to Tat and cocaine due to oxidation of MCU. Since our data suggest that mitochondrial oxidation is dependent in part on MCU-mediated Ca²⁺ uptake, w

SUBMITTER: Natarajaseenivasan K 

PROVIDER: S-EPMC5856787 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature