Shaped by leaky ER: Homeostatic Ca fluxes.

At any moment in time, cells coordinate and balance their calcium ion (Ca) fluxes. The term 'Ca homeostasis' suggests that balancing resting Ca levels is a rather static process. However, direct ER Ca imaging shows that resting Ca levels are maintained by surprisingly dynamic Ca fluxes between the ER Ca store, the cytosol, and the extracellular space. The data show that the ER Ca leak, continuously fed by the high-energy consuming SERCA, is a fundamental driver of resting Ca dynamics. Based on simplistic Ca toolkit models, we discuss how the ER Ca leak could contribute to evolutionarily conserved Ca phenomena such as Ca entry, ER Ca release, and Ca oscillations.