Bax Inhibitor-1-mediated Ca2+leak is decreased by cytosolic acidosis
Author
dc.contributor.author
Kiviluoto, Santeri
Author
dc.contributor.author
Luyten, Tomas
es_CL
Author
dc.contributor.author
Schneider, Lars
es_CL
Author
dc.contributor.author
Lisak, Dmitrij
es_CL
Author
dc.contributor.author
Rojas Rivera, Diego
es_CL
Author
dc.contributor.author
Welkenhuyzen, Kirsten
es_CL
Author
dc.contributor.author
Missaen, Ludwig
es_CL
Author
dc.contributor.author
Smedt, Humbert De
es_CL
Author
dc.contributor.author
Parys, Jan B.
es_CL
Author
dc.contributor.author
Hetz Flores, Claudio
es_CL
Author
dc.contributor.author
Methner, Axel
es_CL
Author
dc.contributor.author
Bultynck, Geert
es_CL
Admission date
dc.date.accessioned
2014-01-15T13:29:58Z
Available date
dc.date.available
2014-01-15T13:29:58Z
Publication date
dc.date.issued
2013
Cita de ítem
dc.identifier.citation
Cell Calcium 54 (2013) 186– 192
en_US
Identifier
dc.identifier.other
DOI: 10.1016/j.ceca.2013.06.002
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/129154
General note
dc.description
Artículo de publicación ISI
en_US
Abstract
dc.description.abstract
tBax Inhibitor-1 (BI-1) is an evolutionarily conserved six-transmembrane domain endoplasmic reticulum(ER)-localized protein that protects against ER stress-induced apoptotic cell death. This function is closelyconnected to its ability to lower steady-state ER Ca2+levels. Recently, we elucidated BI-1’s Ca2+-channelpore in the C-terminal part of the protein and identified the critical amino acids of its pore. Based on theseinsights, a Ca2+-channel pore-dead mutant BI-1 (BI-1D213R) was developed. We determined whether BI-1behaves as a bona fide H+/Ca2+antiporter or as an ER Ca2+-leak channel by investigating the effect of pHon unidirectional Ca2+-efflux rates. At pH 6.8, wild-type BI-1 expression in BI-1−/−cells increased the ERCa2+-leak rate, correlating with its localization in the ER compartment. In contrast, BI-1D231Rexpressionin BI-1−/−, despite its ER localization, did not increase the ER Ca2+-leak rate. However, at pH < 6.8, theBI-1-mediated ER Ca2+leak was blocked. Finally, a peptide representing the Ca2+-channel pore of BI-1promoting Ca2+flux from the ER was used. Lowering the pH from 6.8 to 6.0 completely abolished theability of the BI-1 peptide to mediate Ca2+flux from the ER. We propose that this pH dependence isdue to two aspartic acid residues critical for the function of the Ca2+-channel pore and located in the ERmembrane-dipping domain, which facilitates the protonation of these residues.