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 (Ca(2+)) store, and release of Ca(2+) 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 Ca(2+) efflux from the ER and protects against ER stress. Several mechanisms have been proposed to explain how BI-1 might mediate Ca(2+) efflux from the ER. Chang et al. present structural evidence that a bacterial homolog of BI-1, BsYetJ, is a pH-sensitive Ca(2+) leak channel. This finding not only sheds a new light on ER Ca(2+) efflux mediated by BI-1, but also provides a tentative function for other members of the BI-1 protein family.