Neuronal extracellular vesicles influence the expression, degradation and oligomeric state of fructose 1,6‑bisphosphatase 2 in astrocytes affecting their glycolytic capacity
Hajka D. et al. (2024) Neuronal extracellular vesicles influence the expression, degradation and oligomeric state of fructose 1,6-bisphosphatase 2 in astrocytes affecting their glycolytic capacity. Sci Rep. 14 20932. DOI:10.1038/s41598-024-71560-7
This study investigates the role of neuronal extracellular vesicles (NEVs) in modulating the metabolic activity of astrocytes, with a specific focus on fructose 1,6-bisphosphatase 2 (Fbp2). Fbp2 is an enzyme traditionally involved in gluconeogenesis, but it has also evolved non-catalytic functions such as regulating glycolysis and supporting mitochondrial stability. In hippocampal astrocytes, the presence of NEVs significantly reduces Fbp2 protein levels by promoting its degradation through the Pi3k/Akt pathway. This downregulation is accompanied by alterations in the oligomeric state of Fbp2, favoring its dimeric form, which is crucial for mitochondrial interaction and protection during stress conditions such as calcium influx.
The study also reveals that NEVs reduce the mRNA expression of Fbp2 and alter its oligomeric balance, which in turn increases glycolytic activity in astrocytes. These findings suggest that the communication between neurons and astrocytes via NEVs enables astrocytes to adjust their metabolic functions, particularly increasing lactate production, which is critical for neuronal support. Additionally, NEVs contribute to the stabilization of mitochondrial membrane potential, protecting against calcium-induced mitochondrial dysfunction, an important process for astrocyte-neuron metabolic cooperation.
Keywords: Fructose 1,6-bisphosphatase, neurons, extracellular vesicles, astrocytes, neurons, crosstalk, glycolysis, Fbp2, NEVs, mitochondrial protection
