The Ancient Cell Death Suppressor BAX inhibitor-1

Cell Calcium. 2011 Sep;50(3):251-60. doi: 10.1016/j.ceca.2011.05.005. Epub 2011 Jun 12.

Abstract

Bax inhibitor-1 (BI-1) was initially identified for its ability to inhibit BAX-induced apoptosis in yeast cells and is the founding member of a family of highly hydrophobic proteins localized in diverse cellular membranes. It is evolutionarily conserved and orthologues from plants can substitute for mammalian BI-1 in regard to its anti-apoptotic function suggesting a high degree of functional conservation. BI-1 interacts with BCL-2 and BCL-XL and, similar to these two anti-apoptotic proteins, the effect of BI-1 on cell death involves changes in the amount of Ca(2+) releasable from intracellular stores. However, BI-1 is also a negative regulator of the endoplasmic reticulum stress sensor IRE1 α, it interacts with G-actin and increases actin polymerization, enhances cancer metastasis by altering glucose metabolism and activating the sodium-hydrogen exchanger, and reduces the production of reactive oxygen species through direct interaction with NADPH-P450 reductase. In this contribution, we summarize what is known about the expression, intracellular localization and structure of BI-1 and specifically illuminate its effects on the intracellular Ca(2+) homeostasis and how this might relate to its other functions. We also present a thorough phylogenetic analysis of BI-1 proteins from major phyla together with paralogues from all BI-1 family members.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Calcium / metabolism*
  • Cell Death
  • Endoribonucleases / metabolism
  • Homeostasis
  • Humans
  • Mammals
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • NADPH-Ferrihemoprotein Reductase / metabolism
  • Neoplasms / metabolism
  • Phylogeny
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • bcl-X Protein / metabolism

Substances

  • Actins
  • Apoptosis Regulatory Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • TMBIM6 protein, human
  • bcl-X Protein
  • NADPH-Ferrihemoprotein Reductase
  • ERN1 protein, human
  • Protein-Serine-Threonine Kinases
  • Endoribonucleases
  • Calcium