Autophagy extends lifespan via vacuolar acidification
Authors:Christoph Ruckenstuhl1, Christine Netzberger1, Iryna Entfellner1, Didac Carmona-Gutierrez1, Thomas Kickenweiz1, Slaven Stekovic1, Christina Gleixner1, Christian Schmid1, Lisa Klug1, Ivan Hajnal1, Alice G. Sorgo1, Tobias Eisenberg1, Sabrina Büttner1, Guillermo Marin͂o2-4, Rafal Koziel5, Christoph Magnes6, Frank Sinner6,7, Thomas R. Pieber6,7, Pidder Jansen-Dürr5, Kai-Uwe Fröhlich1, Guido Kroemer2,3,8-11, and Frank Madeo1
doi: 10.15698/mic2014.05.147
Volume 1, pp. 160 to 162, published 05/05/2014.
1 Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.
2 INSERM, U848, F-94805 Villejuif, France.
3 Institut Gustave Roussy, F-94805 Villejuif, France.
4 Université Paris Sud, Paris 11, F-94805 Villejuif, France.
5 Institute for Biomedical Aging Research (IBA), Austrian Academy of Sciences, 6020 Innsbruck, Austria.
6 HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H., 8010 Graz, Austria.
7 Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.
8 Metabolomics Platform, Institut Gustave Roussy, F-94805 Villejuif, France.
9 Centre de Recherche des Cordeliers, F-75005 Paris, France.
10 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, F-75908 Paris, France.
11 Université Paris Descartes, Paris 5, F-75270 Paris, France.
Keywords:
autophagy, methionine restriction, longevity, chronological lifespan, dietary restriction, vacuole, lysosome, acidification.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
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 Marin͂o, Rafal Koziel, Christoph Magnes, Frank Sinner, Thomas R. Pieber, Pidder Jansen-Dürr, Kai-Uwe Fröhlich, Guido Kroemer, and Frank Madeo (2014). Autophagy extends lifespan via vacuolar acidification. Microbial Cell 1(5): 160-162.
© 2014 Ruckenstuhl et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
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).