Fig. 5: Model of metabolic coupling between glia and neurons during starvation.
From: Glia fuel neurons with locally synthesized ketone bodies to sustain memory under starvation
The AMP/ATP ratio decreases during starvation (1), resulting in the activation of AMPK, the major cellular sensor of energy state. AMPK is required to sustain K-AM formation (2). AMPK is required in cortex glia to increase Bmm and CPT1 expression during starvation and to regulate KB transport by Chk (red arrows). During starvation, FAs are mobilized from the internal stores of cortex glia via the action of the lipase Bmm (3). FAs are then imported into the mitochondria via CPT1 and are subsequently oxidized to generate acetyl-CoA, which is used by HMGS for ketogenesis (4). Eventually, KBs are exported from cortex glia via Chk and taken up by neurons via Sln (5). In neurons, during starvation, KBs are used by ACAT1 to generate acetyl-CoA in the mitochondria for energy (6). TCA, tricarboxylic acid cycle; RC, respiratory chain; K, KB; β-Ox, β-oxidation. The metabolic pathways are symbolized by curved arrows, with the pathway position of the enzyme identified in this study appearing in bold.
