Figure 1.

Synaptic functions regulated by endoplasmic reticulum (ER) and mitochondria-dependent Ca²⁺ homeostasis. (A) Schematic diagram depicting the presynaptic functions regulated by ER- and mitochondria-dependent Ca²⁺ dynamics. Ca²⁺ release from ER can modulate spontaneous neurotransmitter release, short-term facilitation (STF) and long-term depression (LTD). Ca²⁺ re-uptake by the ER controls the spontaneous release and STF. Presynaptic mitochondria also play important roles in regulating spontaneous neurotransmitter release, STF and post-tetanic potentiation (PTP) through their ability to regulate Ca²⁺ clearance. (B) A simplified schematic diagram depicting the postsynaptic functions regulated by ER- and mitochondria-dependent Ca²⁺ dynamics. Ca²⁺ release from ER via IP₃-induced Ca²⁺ release (IICR) and Ca²⁺-induced Ca²⁺ release (CICR) controls long-term potentiation (LTP) and LTD. In fact, depending on neuronal and synaptic subtypes, IP₃R and RyR show differential distribution and distinct synaptic functions. Dendritic mitochondrial Ca²⁺ influx can regulate ATP synthesis, Ca²⁺ homeostasis and dendritic development. In non-neuronal cell types, direct Ca²⁺ exchange between ER and mitochondria have been described, but their role in neurons has not yet been documented. IP₃R, IP₃ receptor; RyR, ryanodine receptor; SERCA, smooth endoplasmic reticulum Ca²⁺-ATPase; VGCC, voltage-gated Ca²⁺ channel; PMCA, plasma membrane Ca²⁺-ATPase; NCX: the Na⁺/Ca²⁺ exchanger; mPTP, mitochondrial permeability transition pore; MCU, mitochondrial calcium uniporter; VDAC, voltage-dependent anion channel; mGluR, metabotropic glutamate receptor; GluN, NMDA receptor.