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      Physiological regulation of yeast cell death in multicellular colonies is triggered by ammonia

      research-article
      1 , 2
      The Journal of Cell Biology
      The Rockefeller University Press

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          Abstract

          The existence of programmed cell death (PCD) in yeast and its significance to simple unicellular organisms is still questioned. However, such doubts usually do not reflect the fact that microorganisms in nature exist predominantly within structured, multicellular communities capable of differentiation, in which a profit of individual cells is subordinated to a profit of populations. In this study, we show that some PCD features naturally appear during the development of multicellular Saccharomyces cerevisiae colonies. An ammonia signal emitted by aging colonies triggers metabolic changes that localize yeast death only in the colony center. The remaining population can exploit the released nutrients and survives. In colonies defective in Sok2p transcription factor that are unable to produce ammonia (Váchová, L., F. Devaux, H. Kucerova, M. Ricicova, C. Jacq, and Z. Palková. 2004. J. Biol. Chem. 279:37973–37981), death is spread throughout the whole population, thus decreasing the lifetime of the colony. The absence of Mca1p metacaspase or Aif1p orthologue of mammalian apoptosis-inducing factor does not prevent regulated death in yeast colonies.

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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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            Four deaths and a funeral: from caspases to alternative mechanisms.

            A single family of proteases, the caspases, has long been considered the pivotal executioner of all programmed cell death. However, recent findings of evolutionarily conserved, caspase-independent controlled death mechanisms have opened new perspectives on the biology of cell demise, with particular implications for neurobiology, cancer research and immunological processes.
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              Chronological aging leads to apoptosis in yeast

              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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                Author and article information

                Journal
                J Cell Biol
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                6 June 2005
                : 169
                : 5
                : 711-717
                Affiliations
                [1 ]Institute of Microbiology, Academy of Sciences of the Czech Republic, 142 20 Prague-4, Czech Republic
                [2 ]Department of Genetics and Microbiology, Charles University in Prague, 116 36 Prague-1, Czech Republic
                Author notes

                Correspondence to Zdena Palková: zdenap@ 123456natur.cuni.cz ; or to Libuše Váchová: vachova@ 123456biomed.cas.cz

                Article
                200410064
                10.1083/jcb.200410064
                2171614
                15939758
                f9c96d1c-cc0d-48d2-8734-6e4abe0bb002
                Copyright © 2005, The Rockefeller University Press
                History
                : 12 October 2004
                : 22 April 2005
                Categories
                Research Articles
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                Cell biology
                Cell biology

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