On this week's Journal Club session, Reinoud Maex will talk about his work in the presentation entitled "A mechanism for ATP homeostasis based on activity-dependent synthesis and release of neurotransmitter".

It has long been recognised that many neurotransmitters bear a close relationship, for their synthesis or degradation, to compounds of the mitochondrial Krebs cycle, the central pathway for the production of the energy intermediary adenosine triphosphate (ATP). How neurons maintain an almost constant level of ATP in their cytosol, in spite of varying workloads, is still an outstanding question. Taking the relationship between glutamate (Glu) and alpha-ketoglutarate as an example, a simple metabolic model was built of a Glu- releasing axon terminal. The model included the interconversion between Glu and alpha- ketoglutarate, the accumulation of Glu in synaptic vesicles, and the recycling of Glu through an activity-induced supply of its precursor glutamine by the perisynaptic astrocyte. Assuming near-equilibrium conditions, the model was reduced to two differential equations of the cytosolic concentration of Glu and ATP. This model showed remarkable characteristics: at steady state, irrespective of the workload, the ATP level measured 1.5 mM, and only 4.7 % of the ATP was spent on Glu release and recycling. The speed of ATP homeostasis was determined by the (absolute) amount of ATP the axon spent on vesicular Glu accumulation. Overall, homeostasis came at little cost as it prevented futile ATP production when the workload decreased. These analytical and numerical results indicate that neurotransmitter release may confer to neurons a metabolic advantage in the form of a more accurate ATP homeostasis.

Date: 2024/10/25
Time: 14:00
Location: SP4024A & online