Credit: IMAGE100

Often called the powerhouses of the cell, mitochondria are crucial for neuronal function, and their transport and distribution within neurons must be carefully regulated. Sheng and colleagues now demonstrate the importance of syntaphilin (SNPH) for mitochondrial docking within axons and for synaptic plasticity.

SNPH has previously been linked to presynaptic function; however, its precise role was unknown. The authors showed that SNPH is enriched throughout axonal processes, where it colocalizes with mitochondria. They identified the carboxy-terminal tail of SNPH as the domain that allows it to associate with mitochondria, and also identified a domain (residues 381–469) that localizes it to axons and a specific microtubule-binding domain (residues 130–203) through which it attaches to the cytoskeleton.

To determine the consequences of the association between SNPH and mitochondria, the authors examined mitochondrial motility using time-lapse imaging in cultured hippocampal neurons. They showed that mitochondria that were associated with SNPH mostly remained stationary in axons. Moreover, in hippocampal cultures derived from snph−/− mice, mitochondrial motility was increased and there was a decrease in the total and inter-bouton density of axonal mitochondria. These findings indicate that SNPH has a crucial role in docking mitochondria in axons and close to presynaptic boutons.

Mitochondria are thought to have a role in synaptic plasticity, and changes in their mobility and distribution could influence synaptic function. Electrophysiological recordings from cultured hippocampal neurons revealed enhanced short-term facilitation of snph−/− neurons in response to high-frequency stimulation. Mitochondria have also been linked to calcium buffering in the synapse, and calcium imaging demonstrated an increase in the residual levels of calcium in the presynaptic terminals of snph−/− neurons during prolonged stimulation. This is likely to underlie the observed facilitation.

This study demonstrates the importance for neuronal function of mechanisms that control mitochondrial motility and distribution, and points to SNPH as being one of the key factors responsible for this regulation in axons. The study might also have implications for neurodegenerative diseases that have been linked to defective mitochondrial transport.