Endoplasmic reticulum & mitochondrial calcium homeostasis: The interplay with viruses

Calcium ions (Ca²⁺) act as secondary messengers in a plethora of cellular processes and play crucial role in cellular organelle function and homeostasis. The average resting concentration of Ca²⁺ is nearly 100 nM and in certain cells it can reach up to 1 µM. The high range of Ca²⁺ concentration across the plasma membrane and intracellular Ca²⁺ stores demands a well-coordinated maintenance of free Ca²⁺ via influx, efflux, buffering and storage. Endoplasmic Reticulum (ER) and Mitochondria depend on Ca²⁺ for their function and also serve as major players in intracellular Ca²⁺ homeostasis. The ER-mitochondria interplay helps in orchestrating cellular calcium homeostasis to avoid any detrimental effect resulting from Ca²⁺ overload or depletion. Since Ca²⁺ plays a central role in many biological processes it is an essential component of the virus-host interactions. The large gradient across membranes enable the viruses to easily modulate this buffered environment to meet their needs. Viruses exploit Ca²⁺ signaling to establish productive infection and evade the host immune defense. In this review we will detail the interplay between the viruses and cellular & ER-mitochondrial calcium signaling and the significance of these events on viral life cycle and disease pathogenesis.