Bax inhibitor-1 is a pH-dependent regulator of Ca2+ channel activity in the endoplasmic reticulum
SCIE
SCOPUS
- Title
- Bax inhibitor-1 is a pH-dependent regulator of Ca2+ channel activity in the endoplasmic reticulum
- Authors
- Kim, HR; Lee, GH; Ha, KC; Ahn, T; Moon, JY; Lee, BJ; Cho, SG; Kim, S; Seo, YR; Shin, YJ; Chae, SW; Reed, JC; Chae, HJ
- Date Issued
- 2008-06-06
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLO
- Abstract
- In this study, Bax inhibitor-1 (BI-1) overexpression reduces the ER pool of Ca2+ released by thapsigargin. Cells overexpressing BI-1 also showed lower intracellular Ca2+ release induced by the Ca2+ ionophore ionomycin as well as agonists of ryanodine receptors and inositol trisphosphate receptors. In contrast, cells expressing carboxyl-terminal deleted BI-1 (C Delta-BI-1 cells) displayed normal intracellular Ca2+ mobilization. Basal Ca2+ release rates from the ER were higher in BI-1-overexpressing cells than in control or C Delta-BI-1 cells. We determined that the carboxyl-terminal cytosolic region of BI-1 contains a lysine-rich motif (EKDKKKEKK) resembling the pH-sensing domains of ion channels. Acidic conditions triggered more extensive Ca2+ release from ER microsomes from BI-1-overexpressing cells and BI-1-reconsituted liposomes. Acidic conditions also induced BI-1 protein oligomerization. Interestingly subjecting BI-1 overexpressing cells to acidic conditions induced more Bax recruitment to mitochondria, more cytochrome c release from mitochondria, and more cell death. These findings suggest that BI-1 increases Ca2+ leak rates from the ER through a mechanism that is dependent on pH and on the carboxyl-terminal cytosolic region of the BI-1 protein. The findings also reveal a cell death-promoting phenotype for BI-1 that is manifested under low pH conditions.
- Keywords
- INTRACELLULAR PH; CALCIUM STORES; ION-CHANNEL; CELLS; APOPTOSIS; MACROPHAGES; MECHANISMS; EXPRESSION; BINDING; STRESS
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/22732
- DOI
- 10.1074/jbc.M800075200
- ISSN
- 0021-9258
- Article Type
- Article
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 283, no. 23, page. 15946 - 15955, 2008-06-06
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