Figure 1

The model design.

(a) The schematic diagram of the components and fluxes included in the model. When a cell is stimulated to generate IP₃, IP₃ binds to IP₃R and triggers Ca²⁺ release from the ER through IP₃Rs. The Ca²⁺ in the cytsol can be pumped back into ER by SERCA. (b) IP₃Rs and MCUs in close proximity form a microdomain, a half 3-dimensional cytosolic space separated by ER membrane. A high microdomain [Ca²⁺] ([Ca²⁺]_Mic) can be generated upon opening of IP₃Rs which in turn leads to Ca²⁺ uptake into mitochondria through MCUs. Ca²⁺ is extruded from mitochondria back into the cytosol by NCX. (c) The four-state model of MCU monomer with binding and unbinding rates.