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

György Hajnóczky, György Csordás, Muniswamy Madesh and Pál Pacher

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 neurotransmitter 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.

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