Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells

Significance The neuromuscular junction is the site of transmission of the nerve impulse to the muscle. This finely tuned synapse relies on at least three components: the motor neuron, the muscle fiber, and the Schwann cells, which assist nerve recovery after injury. Using animal neurotoxins to induce an acute and reversible nerve degeneration, we have identified several mitochondrial molecules through which the damaged nerve terminal communicates with nearby cells, activating signaling pathways in Schwann cells involved in nerve regeneration. Among these messengers, hydrogen peroxide appears to be crucial at the initial stages of regeneration, because its inactivation delays the functional recovery of the damaged neuromuscular junction in vivo. These findings provide important indications about the pharmacological treatment of traumatized patients.