The involvement of the vacuole in Bax-induced cell death in Saccharomyces cerevisiae
2003
Dimitrova, I.
Reasoning that at least some of the functions of Bax protein appear to be conserved in yeast, we undertook a functional genetic approach designed to identify yeast genes that are able to inhibit Bax-mediated lethality in S. cerevisiae. As a result, fourteen independent clones were isolated. Most of identified clones showed to be directly or indirectly involved in intracellular protein trafficking events, as well as in vacuolar biogenesis. The identity of the yeast high copy suppressors of the Bax phenotype and the recent identification of a Bax tolerant yeast mutant in the ARL1 gene pointed to a potential involvement of the vacuole. Expression of Bax in yeast is presently shown to affect the integrity of the vacuoles causing disruption and eventual loss of the organelles. In this respect, we assessed the potential involvement of a novel plant Tau class GST, able to inhibit Bax lethality in yeast cells (BI-GST), in the preservation of vacuolar morphology and functionality upon co-expression of Bax protein. The role of the 5 homologous to BI-GST proteins, and mammalian Omega class GSTs (the wild type protein and one with a point mutation in the catalytic site), in vacuolar biogenesis during Bax expression in yeast was also assessed. The data presented reveal pleiotropic effects of the Bax protein in yeast cells and suggests the presence of additional parameters in cell death mechanisms that should receive attention.
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