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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Main Authors: 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
Format: Article
Language:English
Published: Shared Science Publishers OG 2014-05-01
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).
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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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