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Updated: Jul 19, 2025
Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Yeast Bax Inhibitor (Bxi1p/Ybh3p) Is Not Required for the Action of Bcl-2 Family Proteins on Cell Viability
Marek Mentel1, Miroslava Illová1, Veronika Krajčovičová1
1Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská Dolina CH1, Ilkovičova 6, 84215 Bratislava, Slovakia.
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.
Insights
The yeast gene BXI1/YBH3 does not directly impact the function of mammalian BCL-2 family proteins in apoptosis. Deleting BXI1/YBH3 increases yeast sensitivity to acetic acid stress but not other cell death inducers.
Area of Science:
- Cell Biology
- Molecular Biology
- Yeast Genetics
Background:
- Mitochondrial outer membrane permeabilization by BCL-2 family proteins is crucial for apoptosis in mammalian cells.
- Yeast, lacking BCL-2 homologs, can model these proteins' functions when expressed heterologously.
- The yeast gene BXI1/YBH3 encodes an endoplasmic reticulum protein with contradictory roles in Bax activity.
Purpose of the Study:
- To investigate the role of the yeast gene BXI1/YBH3 in regulating cell death pathways.
- To determine if BXI1/YBH3 modulates the activity of pro-apoptotic (Bax, Bak) and anti-apoptotic (Bcl-XL, Bcl-2) mammalian proteins in yeast.
- To assess the impact of BXI1/YBH3 deletion on yeast survival under stress conditions.
Main Methods:
- Heterologous expression of BCL-2 family proteins in yeast.
- Gene deletion of BXI1/YBH3 in yeast.
- Assessing yeast survival after treatment with apoptosis inducers (hydrogen peroxide, acetic acid).
Main Results:
- Deletion of BXI1/YBH3 did not alter yeast sensitivity to heterologously expressed BCL-2 family proteins.
- BXI1/YBH3 deletion increased yeast sensitivity to acetic acid-induced cell death.
- Sensitivity to hydrogen peroxide-induced cell death remained unaffected by BXI1/YBH3 deletion.
Conclusions:
- The yeast gene BXI1/YBH3 does not directly influence the pro- or anti-apoptotic functions of mammalian BCL-2 family proteins.
- BXI1/YBH3 appears to play a role in modulating yeast survival in response to specific stress conditions, such as acetic acid exposure.
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