ATP diffusional gradients are sufficient to maintain bioenergetic homeostasis in synaptic boutons lacking mitochondria

Experimental work on mitochondria distribution in axons indicates that approximately half of the presynaptic release sites do not contain mitochondria. This raises the question of how the boutons that do not contain a mitochondrion are supplied with ATP. We developed a mathematical model that simulates ATP transport by diffusion between a bouton containing a mitochondrion and a bouton lacking a mitochondrion. We investigated whether diffusive transport of ATP is sufficient to support the ATP concentration in a bouton lacking a mitochondrion above the minimum concentration required for endocytosis. Our computational results demonstrate that the difference in ATP concentration between a bouton containing a mitochondrion and a neighboring bouton lacking a mitochondrion is approximately 0.4%. We established that due to diffusion transport, the ATP concentration in the bouton lacking a mitochondrion is 3.75 times larger than the ATP concentration minimally required to support synaptic vesicle release.