The machinery of local Ca²⁺ signalling between sarco-endoplasmic reticulum and mitochondria

Growing evidence suggests that propagation of cytosolic [Ca²⁺] ([Ca²⁺](c)) spikes and oscillations to the mitochondria is important for the control of fundamental cellular functions. Delivery of [Ca²⁺](c) spikes to the mitochondria may utilize activation of the mitochondrial Ca²⁺ uptake sites by the large local [Ca²⁺](c) rise occurring in the vicinity of activated sarco-endoplasmic reticulum (SR/ER) Ca²⁺ release channels. Although direct measurement of the local [Ca²⁺](c) sensed by the mitochondria has been difficult, recent studies shed some light onto the molecular mechanism of local Ca²⁺ communication between SR/ER and mitochondria. Subdomains of the SR/ER are in close contact with mitochondria and display a concentration of Ca²⁺ release sites, providing the conditions for an effective delivery of released Ca²⁺ to the mitochondrial targets. Furthermore, many functional properties of the signalling between SR/ER Ca²⁺ release sites and mitochondrial Ca²⁺ uptake sites, including transient microdomains of high [Ca²⁺], saturation of mitochondrial Ca²⁺ uptake sites by released Ca²⁺, connection of multiple release sites to each uptake site and quantal transmission, are analogous to the features of the coupling between neuro-transmitter release sites and postsynaptic receptors in synaptic transmission. As such, Ca²⁺ signal transmission between SR/ER and mitochondria may utilize discrete communication sites and a closely related functional architecture to that used for synaptic signal propagation between cells.