title: Bax inhibitor-1 is likely a pH-sensitive calcium leak channel, not a H+/Ca2+ exchanger.
abstract: 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.
authors.affiliation: KU Leuven, Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Leuven, Belgium. geert.bultynck@med.kuleuven.be axel.methner@gmail.com.
authors.forename: Geert
authors.initials: G
authors.lastname: Bultynck
authors.affiliation: KU Leuven, Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Leuven, Belgium.
authors.forename: Santeri
authors.initials: S
authors.lastname: Kiviluoto
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn), Johannes Gutenberg University Medical Center Mainz, Department of Neurology, Mainz, Germany. geert.bultynck@med.kuleuven.be axel.methner@gmail.com.
authors.forename: Axel
authors.initials: A
authors.lastname: Methner
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D011510:Proteolipids / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D051017:Apoptosis Regulatory Proteins; D015220:Calcium Channels; D008565:Membrane Proteins; D011510:Proteolipids; C484209:TMBIM6 protein, human; C020485:proteoliposomes; D002118:Calcium