Mitochondrial calcium at the synapse

Abstract

Mitochondria are dynamic organelles, which serve various purposes, including but not limited to the production of ATP and various metabolites, buffering ions, acting as a signaling hub, etc. In recent years, mitochondria are being seen as the central regulators of cellular growth, development, and death. Since neurons are highly specialized cells with a heavy metabolic demand, it is not surprising that neurons are one of the most mitochondria-rich cells in an animal. At synapses, mitochondrial function and dynamics is tightly regulated by synaptic calcium. Calcium influx during synaptic activity causes increased mitochondrial calcium influx leading to an increased ATP production as well as buffering of synaptic calcium. While increased ATP production is required during synaptic transmission, calcium buffering by mitochondria is crucial to prevent faulty neurotransmission and excitotoxicity. Interestingly, mitochondrial calcium also regulates the mobility of mitochondria within synapses causing mitochondria to halt at the synapse during synaptic transmission. In this review, we summarize the various roles of mitochondrial calcium at the synapse.

Keywords: LETM1; MCU; Mitochondrial calcium Efflux; Mitochondrial calcium influx; NCLX; Synaptic calcium; VDAC.