共 44 条
Distinct roles of mitochondria- and ER-localized Bcl-xL in apoptosis resistance and Ca2+ homeostasis
被引:42
作者:

Eno, Colins O.
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机构:
Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA
Univ Louisville, Dept Med, Louisville, KY 40202 USA
Univ Louisville, Dept Pharmacol, Louisville, KY 40202 USA
Univ Louisville, Dept Toxicol, Louisville, KY 40202 USA Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA

Eckenrode, Emily F.
论文数: 0 引用数: 0
h-index: 0
机构:
Rosalind Franklin Univ Med & Sci, Dept Physiol & Biophys, N Chicago, IL 60064 USA Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA

Olberding, Kristen E.
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h-index: 0
机构:
Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA
Univ Louisville, Dept Med, Louisville, KY 40202 USA
Univ Louisville, Dept Pharmacol, Louisville, KY 40202 USA
Univ Louisville, Dept Toxicol, Louisville, KY 40202 USA Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA

Zhao, Guoping
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA
Univ Louisville, Dept Med, Louisville, KY 40202 USA
Univ Louisville, Dept Pharmacol, Louisville, KY 40202 USA
Univ Louisville, Dept Toxicol, Louisville, KY 40202 USA Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA

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Li, Chi
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA
Univ Louisville, Dept Med, Louisville, KY 40202 USA
Univ Louisville, Dept Pharmacol, Louisville, KY 40202 USA
Univ Louisville, Dept Toxicol, Louisville, KY 40202 USA Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA
机构:
[1] Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA
[2] Univ Louisville, Dept Med, Louisville, KY 40202 USA
[3] Univ Louisville, Dept Pharmacol, Louisville, KY 40202 USA
[4] Univ Louisville, Dept Toxicol, Louisville, KY 40202 USA
[5] Rosalind Franklin Univ Med & Sci, Dept Physiol & Biophys, N Chicago, IL 60064 USA
基金:
美国国家卫生研究院;
关键词:
INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS;
BCL-X-L;
ENDOPLASMIC-RETICULUM;
CELL-DEATH;
FAMILY-MEMBERS;
PROTEINS;
MODULATION;
SURVIVAL;
BAX;
REGULATORS;
D O I:
10.1091/mbc.E12-02-0090
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
Bcl-2 proteins are major regulators of cellular responses to intrinsic and extrinsic apoptotic stimuli. Among them, overexpression of the antiapoptotic protein Bcl-x(L) modulates intracellular Ca2+ homeostasis and organelle-specific apoptotic signaling pathways. However, the specific activities of Bcl-x(L) at mitochondria and the endoplasmic reticulum (ER) have not been fully defined. To further explore this, we generated mouse embryonic fibroblast (MEF) cell lines deficient in Bcl-x(L) expression (Bcl-x-KO). Deficiency in Bcl-x(L) expression did not induce compensatory changes in the expression of other Bcl-2 proteins, and Bcl-x-KO MEF cells showed increased sensitivity to various apoptotic stimuli compared with wild-type MEF cells. Targeting Bcl-x(L) at mitochondria but not at the ER restored apoptosis protection in Bcl-x-KO MEF cells to the degree observed in wild-type MEF cells. However, expression of ER-targeted Bcl-x(L) but not mitochondrially targeted Bcl-x(L) was required to restore Ca2+ homeostasis in Bcl-x-KO MEF cells. Of importance, ER-targeted Bcl-x(L) was able to protect cells against death stimuli in the presence of endogenous Bcl-x(L). These data indicate that mitochondrial Bcl-x(L) can regulate apoptosis independently of ER Bcl-x(L) and that when localized exclusively at the ER, Bcl-x(L) impinges on Ca2+ homeostasis but does not affect apoptosis unless Bcl-x(L) is present in additional cellular compartments.
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收藏
页码:2605 / 2618
页数:14
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机构: Geneva Med Sch, Dept Geriatr, CH-1211 Geneva 14, Switzerland

Demaurex, N
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机构: Geneva Med Sch, Dept Geriatr, CH-1211 Geneva 14, Switzerland

Krause, KH
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机构: Geneva Med Sch, Dept Geriatr, CH-1211 Geneva 14, Switzerland