Ceramide triggers metacaspase-independent mitochondrial cell death in yeast

Didac Carmona-Gutierrez, Angela Reisenbichler, Petra Heimbucher, Maria A. Bauer, Ralf J. Braun, Christoph Ruckenstuhl, Sabrina Büttner, Tobias Eisenberg, Patrick Rockenfeller, Kai Uwe Fröhlich, Guido Kroemer, Frank Madeo

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    33 Citations (Scopus)

    Résumé

    The activation of ceramide-generating enzymes, the blockade of ceramide degradation or the addition of ceramide analogs can trigger apoptosis or necrosis in human cancer cells. Moreover, endogenous ceramide plays a decisive role in the killing of neoplastic cells by conventional anticancer chemotherapeutics. Here, we explored the possibility that membrane-permeable C2-ceramide might kill budding yeast (Saccharomyces cerevisiae) cells under fermentative conditions, where they exhibit rapid proliferation and a Warburg-like metabolism that is reminiscent of cancer cells. C2-ceramide efficiently induced the generation of reactive oxygen species (ROS ), as well as apoptotic and necrotic cell death, and this effect was not influenced by deletion of the sole yeast metacaspase. However, C2-ceramide largely failed to cause ROS hypergeneration and cell death upon deletion of the mitochondrial genome. Thus, mitochondrial function is strictly required for C2-ceramide-induced yeast lethality. Accordingly, mitochondria from C2-ceramide-treated yeast cells exhibited major morphological alterations, including organelle fragmentation and aggregation. Altogether, our results point to a pivotal role of mitochondria in ceramide-induced yeast cell death.

    langue originaleAnglais
    Pages (de - à)3973-3978
    Nombre de pages6
    journalCell Cycle
    Volume10
    Numéro de publication22
    Les DOIs
    étatPublié - 15 nov. 2011

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