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Updated: Jun 1, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis
Sabrina Büttner1, Doris Ruli, F-Nora Vögtle
1Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Abstract:
Mitochondrial outer membrane permeabilization is a watershed event in the process of apoptosis, which is tightly regulated by a series of pro- and anti-apoptotic proteins belonging to the BCL-2 family, each characteristically possessing a BCL-2 homology domain 3 (BH3). Here, we identify a yeast protein (Ybh3p) that interacts with BCL-X(L) and harbours a functional BH3 domain. Upon lethal insult, Ybh3p translocates to mitochondria and triggers BH3 domain-dependent apoptosis. Ybh3p induces cell death and disruption of the mitochondrial transmembrane potential via the mitochondrial phosphate carrier Mir1p. Deletion of Mir1p and depletion of its human orthologue (SLC25A3/PHC) abolish stress-induced mitochondrial targeting of Ybh3p in yeast and that of BAX in human cells, respectively. Yeast cells lacking YBH3 display prolonged chronological and replicative lifespans and resistance to apoptosis induction. Thus, the yeast genome encodes a functional BH3 domain that induces cell death through phylogenetically conserved mechanisms.
Insights
Researchers discovered a yeast protein, Ybh3p, with a functional BH3 domain that triggers apoptosis. This discovery reveals conserved cell death mechanisms across species and extends yeast lifespan.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Apoptosis, or programmed cell death, is crucial for development and tissue homeostasis.
- The BCL-2 family of proteins regulates apoptosis by controlling mitochondrial outer membrane permeabilization.
- BH3 domains are key functional motifs within BCL-2 family proteins, mediating interactions and apoptosis signaling.
Purpose of the Study:
- To identify and characterize novel proteins with functional BH3 domains in yeast.
- To investigate the role of Ybh3p in apoptosis and its interaction with mitochondrial components.
- To explore the evolutionary conservation of BH3 domain-mediated apoptosis.
Main Methods:
- Yeast two-hybrid screening to identify interacting proteins.
- Mitochondrial localization studies using fluorescence microscopy.
- Analysis of apoptosis induction and mitochondrial membrane potential.
- Gene deletion and knockdown experiments in yeast and human cells.
Main Results:
- A novel yeast protein, Ybh3p, containing a functional BH3 domain was identified.
- Ybh3p translocates to mitochondria upon lethal insult, inducing apoptosis in a BH3-dependent manner.
- Ybh3p-induced apoptosis and mitochondrial disruption require the mitochondrial phosphate carrier Mir1p.
- Deletion of YBH3 in yeast resulted in increased lifespan and resistance to apoptosis.
Conclusions:
- The yeast genome encodes a functional BH3 domain protein (Ybh3p) that can induce cell death.
- Ybh3p utilizes phylogenetically conserved mechanisms involving mitochondrial targeting and Mir1p for apoptosis induction.
- The findings suggest a conserved role for BH3 domain proteins in regulating cell death across eukaryotes.
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