Autophagy extends lifespan via vacuolar acidification
Methionine restriction (MetR) is one of the rare regimes that prolongs lifespan across species barriers. Using a yeast model, we recently demonstrated that this lifespan extension is promoted by autophagy, which in turn requires vacuolar acidification. Our study is the first to place autophagy as on...
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| Format: | Article |
| Language: | English |
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Shared Science Publishers OG
2014-05-01
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| Series: | Microbial Cell |
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| Online Access: | http://microbialcell.com/researcharticles/autophagy-extends-lifespan-via-vacuolar-acidification/ |
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| author | Christoph Ruckenstuhl Christine Netzberger Iryna Entfellner Didac Carmona-Gutierrez Thomas Kickenweiz Slaven Stekovic Christina Gleixner Christian Schmid Lisa Klug Ivan Hajnal Alice G. Sorgo Tobias Eisenberg Sabrina Büttner Guillermo Marino Rafal Koziel Christoph Magnes Frank Sinner Thomas R. Pieber Pidder Jansen-Dürr Kai-Uwe Fröhlich Guido Kroemer Frank Madeo |
| author_facet | Christoph Ruckenstuhl Christine Netzberger Iryna Entfellner Didac Carmona-Gutierrez Thomas Kickenweiz Slaven Stekovic Christina Gleixner Christian Schmid Lisa Klug Ivan Hajnal Alice G. Sorgo Tobias Eisenberg Sabrina Büttner Guillermo Marino Rafal Koziel Christoph Magnes Frank Sinner Thomas R. Pieber Pidder Jansen-Dürr Kai-Uwe Fröhlich Guido Kroemer Frank Madeo |
| author_sort | Christoph Ruckenstuhl |
| collection | DOAJ |
| description | Methionine restriction (MetR) is one of the rare regimes that prolongs lifespan across species barriers. Using a yeast model, we recently demonstrated that this lifespan extension is promoted by autophagy, which in turn requires vacuolar acidification. Our study is the first to place autophagy as one of the major players required for MetR-mediated longevity. In addition, our work identifies vacuolar acidification as a key downstream element of autophagy induction under MetR, and possibly after rapamycin treatment. Unlike other amino acids, methionine plays pleiotropic roles in many metabolism-relevant pathways. For instance, methionine (i) is the N-terminal amino acid of every newly translated protein; (ii) acts as the central donor of methyl groups through S-adenosyl methionine (SAM) during methylation reactions of proteins, DNA or RNA; and (iii) provides the sulfhydryl groups for FeS-cluster formation and redox detoxification via transsulfuration to cysteine. Intriguingly, MetR causes lifespan extension, both in yeast and in rodents. We could show that in Saccharomyces cerevisiae, chronological lifespan (CLS) is increased in two specific methionine-auxotrophic strains (namely Δmet2 and Δmet15). |
| format | Article |
| id | doaj-art-bc3239da4039470eab23fab7b489917e |
| institution | OA Journals |
| issn | 2311-2638 |
| language | English |
| publishDate | 2014-05-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Microbial Cell |
| spelling | doaj-art-bc3239da4039470eab23fab7b489917e2025-08-20T02:05:20ZengShared Science Publishers OGMicrobial Cell2311-26382014-05-011516016210.15698/mic2014.05.147Autophagy extends lifespan via vacuolar acidificationChristoph Ruckenstuhl0Christine Netzberger1Iryna Entfellner2Didac Carmona-Gutierrez3Thomas Kickenweiz4Slaven Stekovic5Christina Gleixner6Christian Schmid7Lisa Klug8Ivan Hajnal9Alice G. Sorgo10Tobias Eisenberg11Sabrina Büttner12Guillermo Marino13Rafal Koziel14Christoph Magnes15Frank Sinner16Thomas R. Pieber17Pidder Jansen-Dürr18Kai-Uwe Fröhlich19Guido Kroemer20Frank Madeo21Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.INSERM, U848, F-94805 Villejuif, France.Institute for Biomedical Aging Research (IBA), Austrian Academy of Sciences, 6020 Innsbruck, Austria.HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H., 8010 Graz, Austria.HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H., 8010 Graz, Austria.HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H., 8010 Graz, Austria.Institute for Biomedical Aging Research (IBA), Austrian Academy of Sciences, 6020 Innsbruck, Austria.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.INSERM, U848, F-94805 Villejuif, France.Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.Methionine restriction (MetR) is one of the rare regimes that prolongs lifespan across species barriers. Using a yeast model, we recently demonstrated that this lifespan extension is promoted by autophagy, which in turn requires vacuolar acidification. Our study is the first to place autophagy as one of the major players required for MetR-mediated longevity. In addition, our work identifies vacuolar acidification as a key downstream element of autophagy induction under MetR, and possibly after rapamycin treatment. Unlike other amino acids, methionine plays pleiotropic roles in many metabolism-relevant pathways. For instance, methionine (i) is the N-terminal amino acid of every newly translated protein; (ii) acts as the central donor of methyl groups through S-adenosyl methionine (SAM) during methylation reactions of proteins, DNA or RNA; and (iii) provides the sulfhydryl groups for FeS-cluster formation and redox detoxification via transsulfuration to cysteine. Intriguingly, MetR causes lifespan extension, both in yeast and in rodents. We could show that in Saccharomyces cerevisiae, chronological lifespan (CLS) is increased in two specific methionine-auxotrophic strains (namely Δmet2 and Δmet15).http://microbialcell.com/researcharticles/autophagy-extends-lifespan-via-vacuolar-acidification/autophagymethionine restrictionlongevitychronological lifespandietary restrictionvacuolelysosomeacidification |
| spellingShingle | Christoph Ruckenstuhl Christine Netzberger Iryna Entfellner Didac Carmona-Gutierrez Thomas Kickenweiz Slaven Stekovic Christina Gleixner Christian Schmid Lisa Klug Ivan Hajnal Alice G. Sorgo Tobias Eisenberg Sabrina Büttner Guillermo Marino Rafal Koziel Christoph Magnes Frank Sinner Thomas R. Pieber Pidder Jansen-Dürr Kai-Uwe Fröhlich Guido Kroemer Frank Madeo Autophagy extends lifespan via vacuolar acidification Microbial Cell autophagy methionine restriction longevity chronological lifespan dietary restriction vacuole lysosome acidification |
| title | Autophagy extends lifespan via vacuolar acidification |
| title_full | Autophagy extends lifespan via vacuolar acidification |
| title_fullStr | Autophagy extends lifespan via vacuolar acidification |
| title_full_unstemmed | Autophagy extends lifespan via vacuolar acidification |
| title_short | Autophagy extends lifespan via vacuolar acidification |
| title_sort | autophagy extends lifespan via vacuolar acidification |
| topic | autophagy methionine restriction longevity chronological lifespan dietary restriction vacuole lysosome acidification |
| url | http://microbialcell.com/researcharticles/autophagy-extends-lifespan-via-vacuolar-acidification/ |
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