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

Mol Cell. 2004 Aug 13;15(3):355-66. doi: 10.1016/j.molcel.2004.06.038.


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 Ca(2+) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Calcium / physiology
  • Endoplasmic Reticulum / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Mitochondria / physiology
  • Signal Transduction / physiology
  • Time Factors


  • Membrane Proteins
  • Tmbim6 protein, mouse
  • Calcium