Mitochondria determine the sequential propagation of the calcium macrodomains revealed by the super-resolution calcium lantern imaging.

Despite the wide application of super-resolution (SR) microscopy in biological studies of cells, the technology is rarely used to monitor functional changes in live cells. By combining fast spinning disc-confocal structured illumination microscopy (SD-SIM) with loading of cytosolic fluorescent Ca indicators, we have developed an SR method for visualization of regional Ca dynamics and related cellular organelle morphology and dynamics, termed SR calcium lantern imaging. In COS-7 cells stimulated with ATP, we have identified various calcium macrodomains characterized by different types of Ca+ release from endoplasmic reticulum (ER) stores. Finally, we demonstrated various roles of mitochondria in mediating calcium signals from different sources; while mitochondria can globally potentiate the Ca+ entry associated with store release, mitochondria also locally control Ca release from the neighboring ER stores and assist in their refilling processes.