Bax Inhibitor-1-mediated Ca2+ leak is decreased by cytosolic acidosis
Bax Inhibitor-1-mediated Ca2+ leak is decreased by cytosolic acidosis
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DOI：
10.1016/j.ceca.2013.06.002
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发表时间：
2013-09-01
期刊：
影响因子：
4
通讯作者：
Bultynck, Geert
中科院分区：
文献类型：
--
作者：
Kiviluoto, Santeri;Luyten, Tomas;Bultynck, Geert
Bax Inhibitor-1 (BI-1) 是一种进化上保守的六跨膜结构域内质网 (ER) 定位蛋白，可防止 ER 应激诱导的细胞凋亡。该功能与其降低稳态 ER Ca2+ 水平的能力密切相关。最近，我们阐明了BI-1蛋白质C末端部分的Ca2+通道孔，并鉴定了其孔的关键氨基酸。基于这些见解，开发了 Ca2+ 通道孔死突变体 BI-1 (BI-1(D213R))。我们通过研究 pH 对单向 Ca2+ 流出速率的影响来确定 BI-1 是否充当真正的 H+/Ca2+ 反向转运蛋白或 ER Ca2+ 泄漏通道。在 pH 6.8 时，BI-1(-/-) 细胞中野生型 BI-1 的表达增加了 ER Ca2+ 泄漏率，与其在 ER 室中的定位相关。相反，BI-1(-/-)中的BI-1(D213R)表达，尽管其位于ER中，但并没有增加ER Ca2+-泄漏率。然而，在 pH
Bax 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 closely connected to its ability to lower steady-state ER Ca2+ levels. Recently, we elucidated BI-1's Ca2+-channel pore in the C-terminal part of the protein and identified the critical amino acids of its pore. Based on these insights, a Ca2+-channel pore-dead mutant BI-1 (BI-1(D213R)) was developed. We determined whether BI-1 behaves as a bona fide H+/Ca2+ antiporter or as an ER Ca2+-leak channel by investigating the effect of pH on unidirectional Ca2+-efflux rates. At pH 6.8, wild-type BI-1 expression in BI-1(-/-) cells increased the ER Ca2+-leak rate, correlating with its localization in the ER compartment. In contrast, BI-1(D213R) expression in BI-1(-/-), despite its ER localization, did not increase the ER Ca2+-leak rate. However, at pH