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      Chronological aging leads to apoptosis in yeast


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          During the past years, yeast has been successfully established as a model to study mechanisms of apoptotic regulation. However, the beneficial effects of such a cell suicide program for a unicellular organism remained obscure. Here, we demonstrate that chronologically aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen radicals, and show caspase activation. Age-induced cell death is strongly delayed by overexpressing YAP1, a key transcriptional regulator in oxygen stress response. Disruption of apoptosis through deletion of yeast caspase YCA1 initially results in better survival of aged cultures. However, surviving cells lose the ability of regrowth, indicating that predamaged cells accumulate in the absence of apoptotic cell removal. Moreover, wild-type cells outlast yca1 disruptants in direct competition assays during long-term aging. We suggest that apoptosis in yeast confers a selective advantage for this unicellular organism, and demonstrate that old yeast cells release substances into the medium that stimulate survival of the clone.

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          Most cited references15

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          Mechanisms and genes of cellular suicide.

          H Steller (1995)
          Apoptosis is a morphologically distinct form of programmed cell death that plays a major role during development, homeostasis, and in many diseases including cancer, acquired immunodeficiency syndrome, and neurodegenerative disorders. Apoptosis occurs through the activation of a cell-intrinsic suicide program. The basic machinery to carry out apoptosis appears to be present in essentially all mammalian cells at all times, but the activation of the suicide program is regulated by many different signals that originate from both the intracellular and the extracellular milieu. Genetic studies in the nematode Caenorhabditis elegans and in the fruit fly Drosophila melanogaster have led to the isolation of genes that are specifically required for the induction of programmed cell death. At least some components of the apoptotic program have been conserved among worms, insects, and vertebrates.
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            Oxygen Stress: A Regulator of Apoptosis in Yeast

            Oxygen radicals are important components of metazoan apoptosis. We have found that apoptosis can be induced in the yeast Saccharomyces cerevisiae by depletion of glutathione or by low external doses of H2O2. Cycloheximide prevents apoptotic death revealing active participation of the cell. Yeast can also be triggered into apoptosis by a mutation in CDC48 or by expression of mammalian bax. In both cases, we show oxygen radicals to accumulate in the cell, whereas radical depletion or hypoxia prevents apoptosis. These results suggest 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.
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              A caspase-related protease regulates apoptosis in yeast.

              Yeast can undergo cell death accompanied by cellular markers of apoptosis. However, orthologs of classical mammalian apoptosis regulators appeared to be missing from the yeast genome, challenging a common mechanism of yeast and mammalian apoptosis. Here we investigate Yor197w, a yeast protein with structural homology to mammalian caspases, and demonstrate caspase-like processing of the protein. Hydrogen peroxide treatment induces apoptosis together with a caspase-like enzymatic activity in yeast. This response is completely abrogated after disruption and strongly stimulated after overexpression of Yor197w. Yor197w also mediates the death process within chronologically aged cultures, pointing to a physiological role in elimination of overaged cells. We conclude that Yor197w indeed functions as a bona fide caspase in yeast and propose the name Yeast Caspase-1 (YCA1, gene YCA1).

                Author and article information

                J Cell Biol
                The Journal of Cell Biology
                The Rockefeller University Press
                16 February 2004
                : 164
                : 4
                : 501-507
                [1 ]Institute for Physiological Chemistry, University of Tübingen, 72076 Tübingen, Germany
                [2 ]Wilhelm-Schickard Institute for Informatics, University of Tübingen, 72076 Tübingen, Germany
                [3 ]Department of Plant Biology, Carnegie Institution of Washington, Stanford University, Stanford, CA 94305
                [4 ]Institute of Molecular Biology, Biochemistry, and Microbiology, Karl-Franzens University, 8010 Graz, Austria
                [5 ]European Neuroscience Institute Göttingen, 37073 Göttingen, Germany
                Author notes

                Address correspondence to Frank Madeo, Institute for Physiological Chemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany. Tel.: 49-7071-2974184. Fax: 49-7071-295565. email: frank.madeo@ 123456uni-tuebingen.de

                Copyright © 2004, The Rockefeller University Press
                : 3 October 2003
                : 30 December 2003

                Cell biology
                aging; apoptosis; oxygen stress; saccharomyces cerevisiae; yca1
                Cell biology
                aging; apoptosis; oxygen stress; saccharomyces cerevisiae; yca1


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