Browsing by Author "Ligr, Martin"

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    Apoptosis in the yeast saccharomyces cerevisiae : a novel cell death process regulated by the ubiquitin-proteasome system
    (2001) Ligr, Martin; Wolf, Dieter H. (Prof. Dr.)
    Apoptosis is co-regulated by the conserved family of Bcl-2-related proteins, which includes both its agonists (Bax) and antagonists (Bcl-XL). A mutant strain of the yeast Saccharomyces cerevisiae has been shown to express all morphological signs of apoptosis. Overexpression of Bax is lethal in S. cerevisiae, whereas simultaneous overexpression of Bcl-XL rescues the cells. We report that overexpression of mammalian Bax in a S. cerevisiae wild type strain triggers morphological changes similar to those of apoptotic metazoan cells: the loss of asymmetric distribution of plasma membrane phosphatidylserine, plasma membrane blebbing, chromatin condensation and margination, and DNA fragmentation. Simultaneous overexpression of Bcl-XL prevents these changes. We demonstrate that Bax triggers phenotypic alterations in yeast strongly resembling those it causes in metazoan apoptotic cells. Oxygen radicals are important components of metazoan apoptosis. Oxygen radicals accumulate in yeast cells overexpressing Bax, whereas radical depletion or hypoxia prevents apoptosis. This suggests that the generation of oxygen radicals is a key event in the ancestral apoptotic pathway and offer an explanation for the mechanism of Bax-induced apoptosis in the absence of any established apoptotic gene in yeast. I have identified the yeast gene STM1 in an overexpression screen for new proteasomal substrates. Stm1 is a bona fide substrate of the proteasome. It is localized in the perinuclear region and is required for growth in the presence of mutagens. Overexpression in cells with impaired proteasomal degradation leads to cell death accompanied with cytological markers of apoptosis. Cells lacking Stm1 display deficiency in the apoptosis-like cell death process induced by treatment with low concentrations of H2O2. I suggest that Stm1 is involved in the control of the apoptosis-like cell death in yeast.