BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress

Han Jung Chae, Hyung Ryong Kim, Chunyan Xu, Beatrice Bailly-Maitre, Maryla Krajewska, Stan Krajewski, Steven Banares, Janice Cui, Murat Digicaylioglu, Ning Ke, Shinichi Kitada, Edward Monosov, Michael Thomas, Christina L. Kress, Jeremy R. Babendure, Roger Y. Tsien, Stuart A. Lipton, John C. Reed

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Abstract

Bax inhibitor-1 (BI-1) is an evolutionarily conserved endoplasmic reticulum (ER) protein that suppresses cell death in both animal and plant cells. We characterized mice in which the bi-1 gene was ablated. Cells from BI-1-deficient mice, including fibroblasts, hepatocytes, and neurons, display selective hypersensitivity to apoptosis induced by ER stress agents (thapsigargin, tunicamycin, brefeldin A), but not to stimulators of mitochondrial or TNF/Fas-death receptor apoptosis pathways. Conversely, BI-1 overexpression protects against apoptosis induced by ER stress. BI-1-mediated protection from apoptosis induced by ER stress correlated with inhibition of Bax activation and translocation to mitochondria, preservation of mitochondrial membrane potential, and suppression of caspase activation. BI-1 overexpression also reduces releasable Ca2+ from the ER. In vivo, bi-1-/- mice exhibit increased sensitivity to tissue damage induced by stimuli that trigger ER stress, including stroke and tunicamycin injection. Thus, BI-1 regulates a cell death pathway important for cytopreservation during ER stress.

Original languageEnglish (US)
Pages (from-to)355-366
Number of pages12
JournalMolecular Cell
Volume15
Issue number3
DOIs
StatePublished - Aug 13 2004

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Chae, H. J., Kim, H. R., Xu, C., Bailly-Maitre, B., Krajewska, M., Krajewski, S., Banares, S., Cui, J., Digicaylioglu, M., Ke, N., Kitada, S., Monosov, E., Thomas, M., Kress, C. L., Babendure, J. R., Tsien, R. Y., Lipton, S. A., & Reed, J. C. (2004). BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress. Molecular Cell, 15(3), 355-366. https://doi.org/10.1016/j.molcel.2004.06.038