Abstract
In this work, using Saccharomyces cerevisiae as a model, we showed that BetA could inhibit cell proliferation and lead to lethal cytotoxicity accompanying programmed cell death (PCD). Interestingly, it was found that vacuolar protease Pep4p played a pivotal role in BetA-induced S. cerevisiae PCD. The presence of Pep4p reduced the damage of BetA-induced cells. This work implied that BetA may induce cell death of S. cerevisiae through mitochondria-mediated PCD, and the deletion of Pep4 gene possibly accelerated the effect of PCD. The present investigation provided the preliminary research for the complicated mechanism of BetA-induced cell PCD regulated by vacular protease Pep4p and lay the foundation for understanding of the Pep4p protein in an animal model.
Highlights
Yeast is a well-established unicellular eukaryotic model organism used to elucidate the molecular mechanism of apoptotic pathways and has offered new insights into human diseases
These results suggest that Pep4p has a role in apoptotic cell death and the release of a vacuolar protease during regulating cell death is conserved in yeast
To assess the effect of Betulinic acid (BetA) on cell growth, the cells pre-treated with 20 μg/mL BetA for different times were incubated in YPD
Summary
Yeast is a well-established unicellular eukaryotic model organism used to elucidate the molecular mechanism of apoptotic pathways and has offered new insights into human diseases. As is well-acknowledged, yeast vacuoles, membrane-bound acidic organelles, which share many similarities to plant vacuoles, and mammalian lysosomes are involved in the regulation of PCD process. Pep4p translocates to the cytosol with both vacuolar and plasma membrane integrities, which is involved in mitochondrial degradation during acetic acid-induced PCD [28]. These results suggest that Pep4p has a role in apoptotic cell death and the release of a vacuolar protease during regulating cell death is conserved in yeast. We used BetA as the major compound to induce the cell PCD process, firstly showing that vacuolar Pep4p can provide protection for S. cerevisiae cells PCD via a mitochondria-mediated pathway
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