15 results on '"Eisenberg, Tobias"'
Search Results
2. Depletion of endonuclease G selectively kills polyploid cells.
- Author
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Büttner S, Carmona-Gutierrez D, Vitale I, Castedo M, Ruli D, Eisenberg T, Kroemer G, and Madeo F
- Subjects
- DNA, Fungal metabolism, Endodeoxyribonucleases genetics, Gene Deletion, HCT116 Cells, Humans, RNA, Small Interfering metabolism, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae metabolism, Transfection, Cell Death physiology, Endodeoxyribonucleases metabolism, Genes, Fungal physiology, Polyploidy
- Abstract
Endonuclease G is a mitochondrio-nuclear located nuclease with dual-vital and lethal-functions. Besides its role in apoptosis execution, we have recently shown that depletion of endonuclease G leads to necrotic cell death in yeast. Here, we present further mechanistic elucidation of endonuclease G's vital functions. The deletion of the yeast Endonuclease G gene causes the complete elimination of tetraploid cells during exponential growth. Consistently, conditional knockdown of mammalian endonuclease G selectively kills tetraploid but not diploid clones of the human HCT116 colon carcinoma cell line. We conclude that endonuclease G is important for the viability of polyploid mammalian and yeast cells.
- Published
- 2007
- Full Text
- View/download PDF
3. Endonuclease G mediates α‐synuclein cytotoxicity during Parkinson's disease
- Author
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Büttner, Sabrina, Habernig, Lukas, Broeskamp, Filomena, Ruli, Doris, Vögtle, F Nora, Vlachos, Manolis, Macchi, Francesca, Küttner, Victoria, Carmona‐Gutierrez, Didac, Eisenberg, Tobias, Ring, Julia, Markaki, Maria, Taskin, Asli Aras, Benke, Stefan, Ruckenstuhl, Christoph, Braun, Ralf, Van den Haute, Chris, Bammens, Tine, van der Perren, Anke, Fröhlich, Kai‐Uwe, Winderickx, Joris, Kroemer, Guido, Baekelandt, Veerle, Tavernarakis, Nektarios, Kovacs, Gabor G, Dengjel, Jörn, Meisinger, Chris, Sigrist, Stephan J, and Madeo, Frank
- Published
- 2013
- Full Text
- View/download PDF
4. 4,4'Dimethoxychalcone: a natural flavonoid that promotes health through autophagy-dependent and -independent effects
- Author
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Zimmermann, Andreas, Kainz, Katharina, Hofer, Sebastian J., Bauer, Maria A., Schroeder, Sabrina, Dengjel, Jörn, Pietrocola, Federico, Kepp, Oliver, Ruckenstuhl, Christoph, Eisenberg, Tobias, Sigrist, Stephan J., Madeo, Frank, Carmona-Gutierrez, Didac, and Kroemer, Guido
- Subjects
Male ,Aging ,Saccharomyces cerevisiae Proteins ,Longevity ,Myocardial Ischemia ,Cardioprotection ,Saccharomyces cerevisiae ,Mechanistic Target of Rapamycin Complex 1 ,GATA Transcription Factors ,Cell Line ,Mice ,Autophagy ,Animals ,Humans ,flavonoid ,Caenorhabditis elegans ,Cation Transport Proteins ,Angelica ,Flavonoids ,Medicine, East Asian Traditional ,Sirolimus ,GATA ,Cell Death ,Plant Extracts ,Mice, Inbred C57BL ,Drosophila melanogaster ,liver protection ,Gene Expression Regulation ,Commentary ,Signal Transduction ,Transcription Factors - Abstract
The age-induced deterioration of the organism results in detrimental and ultimately lethal pathologies. The process of aging itself involves a plethora of different mechanisms that should be subverted concurrently to delay and/or prevent age- related maladies. We have identified a natural compound, 4,4ʹ-dimethoxychalcone (DMC), which promotes longevity in yeast, worms and flies, and protects mice from heart injury and liver toxicity. Interestingly, both the DMC-mediated lifespan extension and the cardioprotection depend on macroautophagy/autophagy whereas hepatoprotection does not. DMC induces autophagy by inhibiting specific GATA transcription factors (TFs), independently of the TORC1 kinase pathway. The autophagy-independent beneficial effects of DMC might involve its antioxidative properties. DMC treatment results in a phylogenetically conserved, systemic impact on the metabolome, which is most prominently characterized by changes in cellular amino acid composition. Altogether, DMC exerts multiple, geroprotective effects by igniting distinct pathways, and thus represents a potential pharmacological agent that delays aging through multipronged effects.
- Published
- 2019
5. Lipids and cell death in yeast
- Author
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Eisenberg, Tobias and Büttner, Sabrina
- Subjects
cell death ,aging ,apoptosis ,lipids (amino acids, peptides, and proteins) ,Minireviews ,Saccharomyces cerevisiae ,yeast ,lipotoxicity ,Lipid Metabolism ,Lipids ,Models, Biological - Abstract
Understanding lipid-induced malfunction represents a major challenge of today's biomedical research. The connection of lipids to cellular and organ dysfunction, cell death, and disease (often referred to as lipotoxicity) is more complex than the sole lipotoxic effects of excess free fatty acids and requires genetically tractable model systems for mechanistic investigation. We herein summarize recent advances in the field of lipid-induced toxicity that employ the established model system for cell death and aging research of budding yeast Saccharomyces cerevisiae. Studies in yeast have shed light on various aspects of lipotoxicity, including free fatty acid toxicity, sphingolipid-modulated cell death as well as the involvement of cardiolipin and lipid peroxidation in the mitochondrial pathways of apoptosis. Regimens used range from exogenously applied lipids, genetic modulation of lipolysis and triacylglyceride synthesis, variations in sphingolipid/ceramide metabolism as well as changes in peroxisome function by either genetic or pharmacological means. In future, the yeast model of programmed cell death will further contribute to the clarification of crucial questions of lipid-associated malfunction.
- Published
- 2013
6. Lifespan extension by methionine restriction requires autophagy-dependent vacuolar acidification
- Author
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Ruckenstuhl, Christoph, Netzberger, Christine, Entfellner, Iryna, Carmona-Gutierrez, Didac, Kickenweiz, Thomas, Stekovic, Slaven, Gleixner, Christina, Schmid, Christian, Klug, Lisa, Sorgo, Alice G., Eisenberg, Tobias, Büttner, Sabrina, Mariño, Guillermo, Koziel, Rafal, Jansen-Dürr, Pidder, Fröhlich, Kai-Uwe, Kroemer, Guido, and Madeo, Frank
- Subjects
Aging ,autophagy ,Applied Microbiology ,Genes, Fungal ,Longevity ,Yeast and Fungal Models ,Saccharomyces cerevisiae ,QH426-470 ,Research and Analysis Methods ,Microbiology ,Saccharomyces ,acidification ,Model Organisms ,Methionine ,Molecular Cell Biology ,Genetics ,Molecular Biology ,methionine restriction ,Cell Death ,Population Biology ,vacuole ,Organisms ,Fungi ,Biology and Life Sciences ,dietary restriction ,Cell Biology ,Hydrogen-Ion Concentration ,chronological lifespan ,Yeast ,Cell Processes ,Vacuoles ,lysosome ,Organism Development ,Acids ,Gene Deletion ,Research Article ,Developmental Biology - Abstract
Reduced supply of the amino acid methionine increases longevity across species through an as yet elusive mechanism. Here, we report that methionine restriction (MetR) extends yeast chronological lifespan in an autophagy-dependent manner. Single deletion of several genes essential for autophagy (ATG5, ATG7 or ATG8) fully abolished the longevity-enhancing capacity of MetR. While pharmacological or genetic inhibition of TOR1 increased lifespan in methionine-prototroph yeast, TOR1 suppression failed to extend the longevity of methionine-restricted yeast cells. Notably, vacuole-acidity was specifically enhanced by MetR, a phenotype that essentially required autophagy. Overexpression of vacuolar ATPase components (Vma1p or Vph2p) suffices to increase chronological lifespan of methionine-prototrophic yeast. In contrast, lifespan extension upon MetR was prevented by inhibition of vacuolar acidity upon disruption of the vacuolar ATPase. In conclusion, autophagy promotes lifespan extension upon MetR and requires the subsequent stimulation of vacuolar acidification, while it is epistatic to the equally autophagy-dependent anti-aging pathway triggered by TOR1 inhibition or deletion., Author Summary Health- or lifespan-prolonging regimes would be beneficial at both the individual and the social level. Nevertheless, up to date only very few experimental settings have been proven to promote longevity in mammals. Among them is the reduction of food intake (caloric restriction) or the pharmacological administration of caloric restriction mimetics like rapamycin. The latter one, however, is accompanied by not yet fully estimated and undesirable side effects. In contrast, the limitation of one specific amino acid, namely methionine, which has also been demonstrated to elongate the lifespan of mammals, has the advantage of being a well applicable regime. Therefore, understanding the underlying mechanism of the anti-aging effects of methionine restriction is of crucial importance. With the help of the model organism yeast, we show that limitation in methionine drastically enhances autophagy, a cellular process of self-digestion that is also switched on during caloric restriction. Moreover, we demonstrate that this occurs in causal conjunction with an efficient pH decrease in the organelle responsible for the digestive capacity of the cell (the vacuole). Finally, we prove that autophagy-dependent vacuolar acidification is necessary for methionine restriction-mediated lifespan extension.
- Published
- 2014
7. Lipids and cell death in yeast.
- Author
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Eisenberg, Tobias and Büttner, Sabrina
- Subjects
- *
SACCHAROMYCES cerevisiae , *LIPIDS , *CELL death , *BIOLOGICAL research , *LIPOLYSIS , *SPHINGOLIPIDS , *CERAMIDES - Abstract
Understanding lipid-induced malfunction represents a major challenge of today's biomedical research. The connection of lipids to cellular and organ dysfunction, cell death, and disease (often referred to as lipotoxicity) is more complex than the sole lipotoxic effects of excess free fatty acids and requires genetically tractable model systems for mechanistic investigation. We herein summarize recent advances in the field of lipid-induced toxicity that employ the established model system for cell death and aging research of budding yeast Saccharomyces cerevisiae. Studies in yeast have shed light on various aspects of lipotoxicity, including free fatty acid toxicity, sphingolipid-modulated cell death as well as the involvement of cardiolipin and lipid peroxidation in the mitochondrial pathways of apoptosis. Regimens used range from exogenously applied lipids, genetic modulation of lipolysis and triacylglyceride synthesis, variations in sphingolipid/ceramide metabolism as well as changes in peroxisome function by either genetic or pharmacological means. In future, the yeast model of programmed cell death will further contribute to the clarification of crucial questions of lipid-associated malfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
8. A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis.
- Author
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Büttner, Sabrina, Ruli, Doris, Vögtle, F-Nora, Galluzzi, Lorenzo, Moitzi, Barbara, Eisenberg, Tobias, Kepp, Oliver, Habernig, Lukas, Carmona-Gutierrez, Didac, Rockenfeller, Patrick, Laun, Peter, Breitenbach, Michael, Khoury, Chamel, Fröhlich, Kai-Uwe, Rechberger, Gerald, Meisinger, Chris, Kroemer, Guido, and Madeo, Frank
- Subjects
YEAST ,MITOCHONDRIAL membranes ,APOPTOSIS ,CELL death ,LIFE spans ,PHOSPHATES ,CELL differentiation ,AGING - Abstract
Mitochondrial outer membrane permeabilization is a watershed event in the process of apoptosis, which is tightly regulated by a series of pro- and anti-apoptotic proteins belonging to the BCL-2 family, each characteristically possessing a BCL-2 homology domain 3 (BH3). Here, we identify a yeast protein (Ybh3p) that interacts with BCL-X
L and harbours a functional BH3 domain. Upon lethal insult, Ybh3p translocates to mitochondria and triggers BH3 domain-dependent apoptosis. Ybh3p induces cell death and disruption of the mitochondrial transmembrane potential via the mitochondrial phosphate carrier Mir1p. Deletion of Mir1p and depletion of its human orthologue (SLC25A3/PHC) abolish stress-induced mitochondrial targeting of Ybh3p in yeast and that of BAX in human cells, respectively. Yeast cells lacking YBH3 display prolonged chronological and replicative lifespans and resistance to apoptosis induction. Thus, the yeast genome encodes a functional BH3 domain that induces cell death through phylogenetically conserved mechanisms. [ABSTRACT FROM AUTHOR]- Published
- 2011
- Full Text
- View/download PDF
9. Fatty acids trigger mitochondrion-dependent necrosis.
- Author
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Rockenfeller, Patrick, Ring, Julia, Muschett, Vera, Beranek, Andreas, Buettner, Sabrina, Carmona-Gutierrez, Didac, Eisenberg, Tobias, Khoury, Chamel, Rechberger, Gerald, Kohlwein, Sepp D., Kroemer, Guido, and Madeo, Frank
- Published
- 2010
- Full Text
- View/download PDF
10. Induction of autophagy by spermidine promotes longevity.
- Author
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Eisenberg, Tobias, Knauer, Heide, Schauer, Alexandra, Büttner, Sabrina, Ruckenstuhl, Christoph, Carmona-Gutierrez, Didac, Ring, Julia, Schroeder, Sabrina, Magnes, Christoph, Antonacci, Lucia, Fussi, Heike, Deszcz, Luiza, Hartl, Regina, Schraml, Elisabeth, Criollo, Alfredo, Megalou, Evgenia, Weiskopf, Daniela, Laun, Peter, Heeren, Gino, and Breitenbach, Michael
- Subjects
- *
SPERMIDINE , *LIFE change events , *LONGEVITY , *AGING , *CELL death , *POLYAMINES in the body , *LABORATORY mice , *PHYSIOLOGY - Abstract
Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
11. Loss of peroxisome function triggers necrosis
- Author
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Jungwirth, Helmut, Ring, Julia, Mayer, Tanja, Schauer, Alexandra, Büttner, Sabrina, Eisenberg, Tobias, Carmona-Gutierrez, Didac, Kuchler, Karl, and Madeo, Frank
- Subjects
PEROXISOMES ,DEGENERATION (Pathology) ,REACTIVE oxygen species ,CELL death - Abstract
Abstract: Disturbance of peroxisome function can lead to various degenerative diseases during ageing. Here, we show that in yeast deletion of PEX6, encoding a protein involved in a key step of peroxisomal protein import, results in an increased accumulation of reactive oxygen species and an enhanced loss of viability upon acetic acid treatment and during early stationary phase. Cell death of ageing-like yeast cells lacking PEX6 does not depend on the apoptotic key players Yca1p and Aif1p, but instead shows markers of necrosis. Thus, we conclude that loss of peroxisomal function leads to a form of necrotic cell death. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
12. Endonuclease G Regulates Budding Yeast Life and Death
- Author
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Büttner, Sabrina, Eisenberg, Tobias, Carmona-Gutierrez, Didac, Ruli, Doris, Knauer, Heide, Ruckenstuhl, Christoph, Sigrist, Carola, Wissing, Silke, Kollroser, Manfred, Fröhlich, Kai-Uwe, Sigrist, Stephan, and Madeo, Frank
- Subjects
- *
ENDONUCLEASES , *CELL death , *CELL metabolism , *MITOCHONDRIA - Abstract
Summary: Endonuclease G (EndoG) is located in mitochondria yet translocates into the nucleus of apoptotic cells during human degenerative diseases. Nonetheless, a direct involvement of EndoG in cell-death execution remains equivocal, and the mechanism for mitochondrio-nuclear translocation is not known. Here, we show that the yeast homolog of EndoG (Nuc1p) can efficiently trigger apoptotic cell death when excluded from mitochondria. Nuc1p induces apoptosis in yeast independently of metacaspase or of apoptosis inducing factor. Instead, the permeability transition pore, karyopherin Kap123p, and histone H2B interact with Nuc1p and are required for cell death upon Nuc1p overexpression, suggesting a pathway in which mitochondrial pore opening, nuclear import, and chromatin association are successively involved in EndoG-mediated death. Deletion of NUC1 diminishes apoptotic death when mitochondrial respiration is increased but enhances necrotic death when oxidative phosphorylation is repressed, pointing to dual—lethal and vital—roles for EndoG. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
13. Why yeast cells can undergo apoptosis: death in times of peace, love, and war.
- Author
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Büttner, Sabrina, Eisenberg, Tobias, Herker, Eva, Carmona-Gutierrez, Didac, Kroemer, Guido, and Madeo, Frank
- Subjects
- *
APOPTOSIS , *CELL death , *YEAST , *UNICELLULAR organisms , *CELLS - Abstract
The purpose of apoptosis in multicellular organisms is obvious: single cells die for the benefit of the whole organism (for example, during tissue development or embryogenesis). Although apoptosis has also been shown in various microorganisms, the reason for this cell death program has remained unexplained. Recently published studies have now described yeast apoptosis during aging, mating, or exposure to killer toxins (Fabrizio, P., L. Battistella, R. Vardavas, C. Gattazzo, L.L. Liou, A. Diaspro, J.W. Dossen, E.B. Gralla, and V.D. Longo. 2004. J. Cell Biol. 166:1055-1067; Herker, E., H. Jungwirth, K.A. Lehmann, C. Maldener, K.U. Frohlich, S. Wissing, S. Buttner, M. Fehr, S. Sigrist, and F. Madeo. 2004. J. Cell Biol. 164:501-507, underscoring the evolutionary benefit of a cell suicide program in yeast and, thus, giving a unicellular organism causes to die for. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
14. Yeast caspase 1 links messenger RNA stability to apoptosis in yeast.
- Author
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Mazzoni, Cristina, Herker, Eva, Palermo, Vanessa, Jungwirth, Helmut, Eisenberg, Tobias, Madeo, Frank, and Falcone, Claudio
- Subjects
YEAST ,MESSENGER RNA ,APOPTOSIS ,CELL death ,GENES ,AGING ,GENETICS - Abstract
During the past years, yeasts have been successfully established as models to study the mechanisms of apoptotic regulation. We recently showed that mutations in the LSM4 gene, which is involved in messenger RNA decapping, lead to increased mRNA stability and apoptosis in yeast. Here, we show that mitochondrial function and YCA1, which encodes a budding yeast metacaspase, are necessary for apoptosis triggered by stabilization of mRNAs. Deletion of YCA1 in yeast cells mutated in the LSM4 gene prevents mitochondrial fragmentation and rapid cell death during chronological ageing of the culture, diminishes reactive oxygen species accumulation and DNA breakage, and increases resistance to H
2 O2 and acetic acid. mRNA levels in lsm4 mutants deleted for YCA1 are still increased, positioning the Yca1 budding yeast caspase as a downstream executor of cell death induced by mRNA perturbations. In addition, we show that mitochondrial function is necessary for fast death during chronological ageing, as well as in LSM4 mutated and wild-type cells. [ABSTRACT FROM AUTHOR]- Published
- 2005
- Full Text
- View/download PDF
15. Apoptosis in yeast
- Author
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Madeo, Frank, Herker, Eva, Wissing, Silke, Jungwirth, Helmut, Eisenberg, Tobias, and Fröhlich, Kai-Uwe
- Subjects
- *
APOPTOSIS , *YEAST , *EDIBLE fungi , *CELL death , *BIOLOGY - Abstract
Apoptosis is a highly regulated cellular suicide program crucial for metazoan development. However, dysfunction of apoptosis also leads to several diseases. Yeast undergoes apoptosis after application of acetic acid, sugar- or salt-stress, plant antifungal peptides, or hydrogen peroxide. Oxygen radicals seem to be key elements of apoptotic execution, conserved during evolution. Furthermore, several yeast orthologues of central metazoan apoptotic regulators have been identified, such as a caspase and a caspase-regulating serine protease. In addition, physiological occurrence of cell death has been detected during aging and mating in yeast. The finding of apoptosis in yeast, other fungi and parasites is not only of great medical relevance but will also help to understand some of the still unknown molecular mechanisms at the core of apoptotic execution. [Copyright &y& Elsevier]
- Published
- 2004
- Full Text
- View/download PDF
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