Yeast Bax Inhibitor (Bxi1p/Ybh3p) Is Not Required for the Action of Bcl-2 Family Proteins on Cell Viability

Abstract

Permeabilization of mitochondrial membrane by proteins of the BCL-2 family is a key decisive event in the induction of apoptosis in mammalian cells. Although yeast does not have homologs of the BCL-2 family, when these are expressed in yeast, they modulate the survival of cells in a way that corresponds to their activity in mammalian cells. The yeast gene, alternatively referred to as BXI1 or YBH3, encodes for membrane protein in the endoplasmic reticulum that was, contradictorily, shown to either inhibit Bax or to be required for Bax activity. We have tested the effect of the deletion of this gene on the pro-apoptotic activity of Bax and Bak and the anti-apoptotic activity of Bcl-XL and Bcl-2, as well on survival after treatment with inducers of regulated cell death in yeast, hydrogen peroxide and acetic acid. While deletion resulted in increased sensitivity to acetic acid, it did not affect the sensitivity to hydrogen peroxide nor to BCL-2 family members. Thus, our results do not support any model in which the activity of BCL-2 family members is directly affected by BXI1 but rather indicate that it may participate in modulating survival in response to some specific forms of stress.