ATP Made by Mitochondria Diffuse in Nerve Cells to Maintain Energy Levels for Synaptic Transmission^♦

The Role of Mitochondrially Derived ATP in Synaptic Vesicle Recycling

^♦ See referenced article, J. Biol. Chem. 2015, 290, 22325–22336

Nerve cells communicate with each other at synapses. The synaptic release of neurotransmitters requires a lot of energy, but not much is known about how this energy is generated. Synapses occur at knob-like swellings, known as boutons, but less than half of these contain mitochondria, the powerhouses of cells. In this Paper of the Week, a team led by Ken Nakamura at the Gladstone Institute of Neurological Disease developed assays that allowed them to demonstrate that ATP molecules made in mitochondria of axons were dispersed among boutons. In this manner, neurons maintain the ATP levels needed for energy-intensive synaptic vesicle recycling at boutons, even if some of the boutons lack mitochondria. The investigators went on to show that synaptic vesicle cycling decreased because of a loss of ATP made by mitochondria in cellular model for a neurodegenerative disorder called Leigh's disease. The authors conclude, “ATP diffuses rapidly in axons to support synaptic vesicle recycling. Mitochondrial dysfunction decreases synaptic energy and impairs function.”

Mitochondria-derived ATP diffuses from adjacent boutons to maintain synaptic function in boutons lacking mitochondria.

• © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.