GATOR1 Signaling Defects Promote Astrocytic Metabolic Rewiring and Excitatory Neurotransmitter Cycling

ABSTRACT: GATOR1 is an evolutionarily-conserved negative regulator of mTORC1-dependent signal transduction with pathogenic mutations linked to epilepsy, infantile spasms, and autism spectrum disorders. While a biochemical role of GATOR1 in amino acid-signaling is established, its cell-type specific contributions within the brain remain poorly defined. Here, we show that loss of GATOR1 function in astrocytic cells disrupts mitochondrial metabolism, with a selective dysfunction of the electron transport chain Complex II leading to elevated reactive oxygen species (ROS) and redox imbalance. These changes are accompanied by compensatory increases in antioxidant regulatory systems including superoxide dismutase, but remain insufficient to ameliorate the increased ROS. GATOR1-deficient astrocytes show me

SUBMITTER: Imane Hadj-Aissa 

PROVIDER: S-SCDT-10_1038-S44319-026-00846-W | biostudies-other |

REPOSITORIES: biostudies-other