Mitochondria at the neuronal presynapse in health and disease

Mitochondria may be actively recruited to presynapses to supply energy, buffer calcium and, potentially, fulfil other functions. In this Review, Devine and Kittler examine the importance of this presynaptic population of mitochondria in the maintenance of neuronal homeostasis and how dysfunctional presynaptic mitochondria might contribute to neurodegenerative diseases. Synapses enable neurons to communicate with each other and are therefore a prerequisite for normal brain function. Presynaptically, this communication requires energy and generates large fluctuations in calcium concentrations. Mitochondria are optimized for supplying energy and buffering calcium, and they are actively recruited to presynapses. However, not all presynapses contain mitochondria; thus, how might synapses with and without mitochondria differ? Mitochondria are also increasingly recognized to serve additional functions at the presynapse. Here, we discuss the importance of presynaptic mitochondria in maintaining neuronal homeostasis and how dysfunctional presynaptic mitochondria might contribute to the development of disease.