Isolation of yeast genes restoring sensitivity to bax tolerant mutants. Bax lethality in yeast affects the vacuoles in addition to mitochondria in a distinct manner
2003
Mwew, C. M.
The world ends not with bang but with a whimper. Programmed cell death is the main form of cell death in living organisms. It is genetically controlled and plays an important role in the development and regulation of tissues in organisms. Previous studies have identified various proteins among the factors to be involved in PCD. These are the Bcl-2 and caspaces families. Bax proapopptotic protein is a member of the Bcl-2 family, which was discovered in mammalian cells having some of its functions conserved in yeast. In this study, Saccharomyces cerevisiae was used as a model to investigate genes that are able to reconstitute Bax-mediated lethality. Yeast mutants tolerant to Bax expression generated from the mutagenising of two yeast strains BY4741 and EGY48 were used. Complementation cloning of a yeast genomic library in R6, a recessive mutant also defective in autophagy, revealed nine independent clones restoring sensitivity to Bax-lethality. The identification gave on one of the clones as cytochrome C oxidase found in the mitochondria. Others were TSA2 involved in redox regulation, SOP4 in transport of cellular materials from ER to Gogli, STE5 in scaffold protein activity and DSS4 in yeast secretory pathway. Most of the genes are shown to be involved directly or indirectly in intracellular protein trafficking events, as well as in vacuolar biogenesis. This study, which mainly concentrates on mitochondria and vacuole, confirmed vacuole disruption under Bax expression, with very little effect being observed on mitochondria for the mutant strains examined.
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