Bax Inhibitor-1 Is Likely a pH-Sensitive Calcium Leak Channel, Not a H+/Ca2+ Exchanger

The endoplasmic reticulum (ER) plays a key role in the synthesis, folding, and sorting of proteins, and disturbances of this delicate system can cause cell death. The ER also serves as the major intracellular calcium (Ca2+) store, and release of Ca2+ from this store controls diverse cellular functions. At the interface of both these functions of the ER is Bax inhibitor-1 (BI-1), an evolutionarily conserved multifunctional protein that mediates Ca2+ efflux from the ER and protects against ER stress. Several mechanisms have been proposed to explain how BI-1 might mediate Ca2+ efflux from the ER. Chang et al. present structural evidence that a bacterial homolog of BI-1, BsYetJ, is a pH-sensitive Ca2+ leak channel. This finding not only sheds a new light on ER Ca2+ efflux mediated by BI-1, but also provides a tentative function for other members of the BI-1 protein family.