Mitochondria at the neuronal presynapse in health and disease

• Published in: Nature reviews. Neuroscience Vol. 19; no. 2; pp. 63 - 80
• Main Authors: Devine, Michael J., Kittler, Josef T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2018; Nature Publishing Group
• Subjects: 13; 631/378/1689/1285; 631/378/1689/132/1283; 631/378/1689/1718; 631/378/87; 631/80/642/333; Analysis; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedicine; Calcium buffering; Calcium Signaling - physiology; Health aspects; Homeostasis; Homeostasis - physiology; Humans; Methods; Mitochondria; Mitochondria - physiology; Mitochondrial DNA; Neurobiology; Neurons - physiology; Neurophysiology; Neurosciences; Presynapse; Presynaptic Terminals - physiology; review-article; Synaptic Transmission - physiology; Synaptic vesicles; United Kingdom
• ISSN: 1471-003X; 1471-0048; 1469-3178
• DOI: 10.1038/nrn.2017.170

Key Points
Synaptic communication within the nervous system is a highly energy-demanding process that is tightly regulated by Ca
2+
signalling
Mitochondria are ideally suited to provide energy to power synaptic function and buffer Ca
2+
, and they are actively recruited to and from synapses
Presynaptic mitochondria are important for providing ATP to support prolonged synaptic activity
Presynaptic mitochondria are also capable of buffering presynaptic Ca
2+
signals, thereby modulating neurotransmission and potentially placing an upper limit on synaptic activity
Greater computational flexibility might be afforded by varying the mitochondrial occupancy of presynapses
Dysfunction of presynaptic mitochondria could contribute to neurodegeneration by impairing synaptic homeostasis
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.